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1. Tumor Stiffening, a Key Determinant of Tumor Progression, is Reversed by Nanomaterial-Induced Photothermal Therapy

Author: Marangon, Iris, Silva, Amanda, Guilbert, Thomas, Kolosnjaj-Tabi, Jelena, Marchiol, Carmen, Natkhunarajah, Sharuja, Chamming's, Foucault, Ménard-Moyon, Cécilia, Bianco, Alberto, Gennisson, Jean-Luc, Renault, Gilles, Gazeau, Florence, Matière et Systèmes Complexes (MSC (UMR_7057)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Immunopathologie et chimie thérapeutique (ICT), Centre National de la Recherche Scientifique (CNRS)-Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Institut Langevin - Ondes et Images (UMR7587) (IL), Sorbonne Université (SU)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Paris (UP)-Centre National de la Recherche Scientifique (CNRS), ANR-10-NANO-0008,NANOTHER,Hybrides multifonctionnels à base de nanotubes de carbone et de nanoparticules d'oxyde de fer fonctionnalisés pour des applications en imagerie et en thérapie(2010), ANR-10-LABX-0096,SEAM,Science and Engineering for Advanced Materials and devices(2010), Bos, Mireille, NANOTECHNOLOGIES ET NANOSYSTEMES - Hybrides multifonctionnels à base de nanotubes de carbone et de nanoparticules d'oxyde de fer fonctionnalisés pour des applications en imagerie et en thérapie - - NANOTHER2010 - ANR-10-NANO-0008 - P2N - VALID, Science and Engineering for Advanced Materials and devices - - SEAM2010 - ANR-10-LABX-0096 - LABX - VALID, Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Matière et Systèmes Complexes ( MSC ), Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Paris-Centre de Recherche Cardiovasculaire ( PARCC - U970 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Immunopathologie et chimie thérapeutique ( ICT ), Institut de biologie moléculaire et cellulaire ( IBMC ), Université de Strasbourg ( UNISTRA ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Strasbourg ( UNISTRA ) -Centre National de la Recherche Scientifique ( CNRS ) -Centre National de la Recherche Scientifique ( CNRS ), Institut Langevin ondes et images, Centre National de la Recherche Scientifique ( CNRS ) -ESPCI ParisTech-Université Paris Diderot - Paris 7 ( UPD7 ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ), ANR-10-NANO-0008,NANOTHER,Hybrides multifonctionnels à base de nanotubes de carbone et de nanoparticules d’oxyde de fer fonctionnalisés pour des applications en imagerie et en thérapie ( 2010 ), and ANR-11-LABX-086 - ANR-11-IDEX-05-02,LabEx SEAM,Science and Engineering for Advanced Materials and devices
Subjects: elastography, photothermal therapy, administration & dosage, Antineoplastic Agents, methods, Mice, pathology, therapy, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Animals, cancer, tumor microenvironment, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, carbon nanotubes, Nanotubes, Carbon, Lasers, Hyperthermia, Induced, Nanostructures, Disease Models, Animal, Photochemotherapy, Carcinoma, Squamous Cell, Elasticity Imaging Techniques, Heterografts, Chimie/Chimie thérapeutique, Research Paper
Abstract: Tumor stiffening, stemming from aberrant production and organization of extracellular matrix (ECM), has been considered a predictive marker of tumor malignancy, non-invasively assessed by ultrasound shear wave elastography (SWE). Being more than a passive marker, tumor stiffening restricts the delivery of diagnostic and therapeutic agents to the tumor and per se could modulate cellular mechano-signaling, tissue inflammation and tumor progression. Current strategies to modify the tumor extracellular matrix are based on ECM-targeting chemical agents but also showed deleterious systemic effects. On-demand excitable nanomaterials have shown their ability to perturb the tumor microenvironment in a spatiotemporal-controlled manner and synergistically with chemotherapy. Here, we investigated the evolution of tumor stiffness as well as tumor integrity and progression, under the effect of mild hyperthermia and thermal ablation generated by light-exposed multi-walled carbon nanotubes (MWCNTs) in an epidermoid carcinoma mouse xenograft. SWE was used for real-time mapping of the tumor stiffness, both during the two near infrared irradiation sessions and over the days after the treatment. We observed a transient and reversible stiffening of the tumor tissue during laser irradiation, which was lowered at the second session of mild hyperthermia or photoablation. In contrast, over the days following photothermal treatment, the treated tumors exhibited a significant softening together with volume reduction, whereas non-treated growing tumors showed an increase of tumor rigidity. The organization of the collagen matrix and the distribution of CNTs revealed a spatio-temporal correlation between the presence of nanoheaters and the damages on collagen and cells. This study highlights nanohyperthermia as a promising adjuvant strategy to reverse tumor stiffening and normalize the mechanical tumor environment. journal article research support, non-u.s. gov't 2017 2017 01 01 imported
Published: 2017
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2. Revisiting the JOQUER trial: stratification of primary Sjögren’s syndrome and the clinical and interferon response to hydroxychloroquine

Author: Dennis Lendrem, Iris L A Bodewes, Nadia Howard-Tripp, Jessica Tarn, Marjan A. Versnel, Alexis Collins, Raphaèle Seror, Jacques-Eric Gottenberg, Xavier Mariette, James Wason, Wan-Fai Ng, Newcastle University [Newcastle], Newcastle Upon Tyne Hospitals NHS Foundation Trust, Erasmus University Medical Center [Rotterdam] (Erasmus MC), CHU Strasbourg, Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Immunopathologie et chimie thérapeutique (ICT), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Bicêtre, seror, raphaele, and Immunology
Subjects: medicine.medical_specialty, [SDV]Life Sciences [q-bio], Immunology, Placebo, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Interferon, Internal medicine, medicine, Immunology and Allergy, Clinical Trials, 030212 general & internal medicine, Depression (differential diagnoses), 030203 arthritis & rheumatology, business.industry, Repeated measures design, Hydroxychloroquine, [SDV] Life Sciences [q-bio], Sjögren’s syndrome, Anxiety, Sjögren's syndrome, Sjogren s, medicine.symptom, business, medicine.drug
Abstract: To re-analyse the clinical outcomes and interferon (IFN) activity data from the JOQUER trial, a phase III trial investigating hydroxychloroquine (HCQ) in patients with primary Sjögren’s syndrome (pSS), after stratifying patients into putative pathobiological subgroups utilizing the Newcastle Sjögren’s Stratification Tool (NSST) based on patient-reported symptoms of dryness, pain, fatigue, anxiety and depression. 107 patients were assigned to one of four subgroups using NSST at baseline—the high symptom burden (HSB), pain dominant with fatigue (PDF), dryness dominant with fatigue (DDF) and low symptom burden (LSB). Endpoints were re-analysed after stratification, testing for treatment differences within subgroups and adjusting for baseline differences using a repeated measures covariate model. The HSB subgroup (n = 32) showed a relative improvement in ESSPRI of 1.49 points (95% CI 0.54–2.43; p = 0.002) within 12 weeks in patients taking HCQ compared to placebo, with no further changes after 24 weeks. For the LSB subgroup (n = 14), the ESSPRI worsened in the placebo but not the HCQ arm after 12 weeks (mean difference 1.44, 95% CI 0.05–2.83, p = 0.042). Neither the HSB nor the LSB patients showed significant changes in IFN activity at 24 weeks. There were no significant differences in ESSPRI in the PDF (n = 39) and DDF (n = 22) patients taking HCQ. However, significant reductions in overall IFN score at 24 weeks were seen in both PDF (difference at 24 weeks; 6.41, 95% CI, 2.48–10.34, p = 0.002) and DDF (difference at 24 weeks; 7.23, 95% CI, 1.85–12.6, p = 0.009) without improvement in ESSPRI. Although the JOQUER trial reported no overall benefit from HCQ in pSS patients, stratification suggests that both HSB and LSB subgroups may respond to HCQ. However, these patients may benefit through mechanisms other than the reduction of IFN activities.
Published: 2021
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3. Reaction between Graphene Oxide and Intracellular Glutathione Affects Cell Viability and Proliferation

Author: Baojin Ma, Alberto Bianco, Yuta Nishina, Shi Guo, Immunopathologie et chimie thérapeutique (ICT), Institut de biologie moléculaire et cellulaire (IBMC), and Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Materials science, oxidation, Cell Survival, reduction, Biocompatible Materials, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Oxidative phosphorylation, medicine.disease_cause, ACS Applied Materials & Interfaces Manuscript ID am-2020-17523u.R2 carbon nanomaterial, Cell Line, chemistry.chemical_compound, medicine, Humans, General Materials Science, Viability assay, Cytotoxicity, ComputingMilieux_MISCELLANEOUS, Cell Proliferation, chemistry.chemical_classification, Reactive oxygen species, Cell growth, Glutathione, Cell biology, Oxidative Stress, chemistry, cancer cells, Graphite, Chimie/Chimie thérapeutique, Reactive Oxygen Species, Intracellular, Oxidative stress, HeLa Cells
Abstract: Graphene oxide (GO) is currently developed for biomedical applications as a promising nanoplatform for drug delivery, phototherapy, and biosensing. As a consequence, its safety and cytotoxicity issues have attracted extensive attention. It has been demonstrated that GO causes an increase of intracellular oxidative stress, likely leading to its cytotoxicity and inhibition of cell proliferation. Being one of the main reductive intracellular substances, glutathione (GSH) is vital in the regulation of the oxidative stress level to maintain normal cellular functions. In this study, we found that GSH could be oxidized to GSSG by GO, leading to the formation of reduced GO (rGO). GSH depletion affects the intracellular reductive/oxidative balance, provoking the increase of the reactive oxygen species level, sequentially inhibiting cell viability and proliferation. Therefore, the reaction between GO and GSH provides a new perspective to explain the origin of GO cytotoxicity.
Published: 2021
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4. Strategic Outlook toward 2030: Japan's research for allergy and immunology – Secondary publication

Author: Masayuki Amagai, Nobuyuki Hizawa, Mitsuhiro Okano, Mayumi Tamari, Hideaki Morita, Takeya Adachi, Komei Ito, Motohiro Ebisawa, Koichiro Asano, Shigeharu Fujieda, Hidehisa Saeki, Akemi Yoshimoto, Kenji Kabashima, Mariko Sonobe, Hiroyuki Arai, Kenji Kondo, Atsuki Fukushima, Eiichi Uchio, Mizuho Nagao, Satoshi Konno, Kazuhiko Yamamoto, Ken Ishii, Keigo Kainuma, Kenji Matsumoto, Japan Agency for Medical Research and Development (AMED), Immunopathologie et chimie thérapeutique (ICT), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Tokai University, Keio University School of Medicine [Tokyo, Japan], International University of Health and Welfare (IUHW), Graduate School of Medicine and Faculty of Medicine Kyoto University, Nippon Medical School [Tokyo, Japon], Université de Tsukuba = University of Tsukuba, Kochi University, RIKEN Center for Integrative Medical Sciences [Yokohama] (RIKEN IMS), RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), and The Jikei University School of Medicine
Subjects: 0301 basic medicine, lcsh:Immunologic diseases. Allergy, Biomedical Research, Allergy, Process (engineering), media_common.quotation_subject, [SDV]Life Sciences [q-bio], Immunology, Strategy, Basic law, 03 medical and health sciences, 0302 clinical medicine, Japan, Political science, Allergy and Immunology, Realm, Health care, Hypersensitivity, Immunology and Allergy, Humans, MHLW, Digitization, media_common, Strategic planning, business.industry, General Medicine, 3. Good health, Identification (information), 030104 developmental biology, 030228 respiratory system, business, lcsh:RC581-607, Welfare
Abstract: Strategic Outlook toward 2030: Japan's Research for Allergy and Immunology (Strategy 2030) is the national research strategy based on Japan's Basic Law on Measures Against Allergic Diseases, a first of its kind worldwide. This strategy was established by a multi-disciplinary committee consisting of administrators of the Ministry of Health, Labour and Welfare of Japan, young and senior experts from various research societies and associations, and representatives of patient and public groups. Whereas the issues of transition, integration, and international collaboration have yet to be solved in this research realm in Japan, identification of unmet needs, digitization of information and transparent procedures, and strategic planning for complex problems (a process dubbed MIERUKA by the Toyota Way) are crucial to share and tackle the same vision and goals. The committee developed three specific actions focusing on preemptive treatment, interdisciplinarity and internationality, and life stage. The real success of Strategy 2030 is made by the spontaneous contributions of doctors, dentists, veterinarians, and other medical professionals; basic and clinical research scientists, research supporters, and pharmaceutical/medical device companies; manufacturers of food, healthcare, and home appliances; and patients, their families, and the public. The hope is to establish a stable society in which people can live long, healthy lives, as free as possible from allergic and immunological diseases, at each individual life stage. This article is based on a Japanese review first reported in Arerugi, introduces the developmental process and details of Strategy 2030.
Published: 2020
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5. Auto-immunité et médecine personnalisée

Author: Thierry Martin, Aurélien Guffroy, Vincent Gies, Immunopathologie et chimie thérapeutique (ICT), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), and CCSD, Accord Elsevier
Subjects: 030203 arthritis & rheumatology, 0303 health sciences, medicine.medical_specialty, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Gastroenterology, Precision medicine, 03 medical and health sciences, 0302 clinical medicine, Internal Medicine, medicine, Medical physics, Personalized medicine, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030304 developmental biology
Published: 2020
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6. Le microenvironnement sinusoïdal contrôle la mise en place et la différenciation des macrophages ganglionnaires

Author: Vincent Flacher, Christopher G. Mueller, Abdouramane Camara, Immunopathologie et chimie thérapeutique (ICT), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Queen's cancer reserach institute, Immunologie et chimie thérapeutiques (ICT), and Cancéropôle du Grand Est-Centre National de la Recherche Scientifique (CNRS)
Subjects: Cell physiology, 0303 health sciences, business.industry, [SDV]Life Sciences [q-bio], Cellular differentiation, Niche, General Medicine, Biology, General Biochemistry, Genetics and Molecular Biology, Cell biology, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, Text mining, Immunity, medicine, business, Lymph node, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 030215 immunology
Abstract: International audience; No abstract available
Published: 2020
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7. Rational Chemical Multifunctionalization of Graphene Interface Enhances Targeted Cancer Therapy

Author: Gonzalo Abellán, Eijiro Miyako, Giacomo Reina, Alberto Bianco, Yue Yu, Matteo Andrea Lucherelli, Immunopathologie et chimie thérapeutique (ICT), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut de biologie moléculaire et cellulaire (IBMC), and Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: multifunctionalization, Carbon materials, Cancer therapy, Antineoplastic Agents, Nanotechnology, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, 010402 general chemistry, 01 natural sciences, Catalysis, law.invention, Drug Delivery Systems, law, Cell Line, Tumor, Neoplasms, medicine, Humans, cancer, Doxorubicin, diazonium salts, Càncer, Materials, ComputingMilieux_MISCELLANEOUS, graphite, 010405 organic chemistry, Graphene, Chemistry, Cancer, General Medicine, General Chemistry, Photothermal therapy, medicine.disease, 0104 chemical sciences, Drug delivery, Cancer cell, Surface modification, medicine.drug
Abstract: The synthesis of a drug delivery platform based on graphene was achieved through a step‐by‐step strategy of selective amine deprotection and functionalization. The multifunctional graphene platform, functionalized with indocyanine green, folic acid, and doxorubicin showed an enhanced anticancer activity. The remarkable targeting capacity for cancer cells in combination with the synergistic effect of drug release and photothermal properties prove the great advantage of a combined chemo‐ and phototherapy based on graphene against cancer, opening the doors to future therapeutic applications of this type of material.
Published: 2020
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8. Quelle taxonomie des maladies inflammatoires en rhumatologie ?: Le concept de psoutte

Author: Messer, Laurent, Felten, Renaud, Duret, Pierre-Marie, Gottenberg, Jacques Eric, Widawski, Laura, Meyer, Alain, Lomo Myazhiom, Aggée Célestin, Spielmann, Lionel, Sibilia, Jean, Service de rhumatologie [Strasbourg], CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Immunopathologie et chimie thérapeutique (ICT), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Dynamiques européennes (DynamE), and Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SDV]Life Sciences [q-bio]
Abstract: International audience; La pratique clinique de la médecine nécessite la reconnaissance de la maladie dont souffre le patient par le médecin. Pour cela, celui-ci rationnalise les signes permettant d’isoler une entité réaliste et de la classer dans la nosologie de référence. Contrairement à d’autres pratiques, le modèle biomédical utilise la méthodologie scientifique du recensement, dans une logique de classification pour définir les maladies. Du fait de son processus de simplification, ce modèle néglige les cas de transition ou les cas complexes. En rhumatologie, ce raisonnement classifiant est mis à l’épreuve par le manque d’objectivité et de spécificité des éléments sur lesquels s’appuie le clinicien pour construire le diagnostic, mais aussi par la complexité des mécanismes physiopathologiques des maladies rhumatismales. Ces maladies peuvent en effet se confondre ou s’intriquer, pour aboutir alors à la description de nouvelles entités non envisagées dans les classifications. Nous présentons dans cette revue les difficultés rencontrées au cours de l’exercice de la médecine dans ces contextes, et comment, à partir d’un cas concret, vécu, celles-ci peuvent donner naissance à la proposition d’un nouveau taxon1.
Published: 2021
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9. A human liver cell-based system modeling a clinical prognostic liver signature for therapeutic discovery

Author: Crouchet, Emilie, Bandiera, Simonetta, Fujiwara, Naoto, Li, Shen, El Saghire, Hussein, Fernández-Vaquero, Mirian, Riedl, Tobias, Sun, Xiaochen, Hirschfield, Hadassa, Jühling, Frank, Zhu, Shijia, Roehlen, Natascha, Ponsolles, Clara, Heydmann, Laura, Saviano, Antonio, Qian, Tongqi, Venkatesh, Anu, Lupberger, Joachim, Verrier, Eloi R., Sojoodi, Mozhdeh, Oudot, Marine A., Duong, François H. T., Masia, Ricard, Wei, Lan, Thumann, Christine, Durand, Sarah C., González-Motos, Victor, Heide, Danijela, Hetzer, Jenny, Nakagawa, Shigeki, Ono, Atsushi, Song, Won-Min, Higashi, Takaaki, Sanchez, Roberto, Kim, Rosa S., Bian, C. Billie, Kiani, Karun, Croonenborghs, Tom, Subramanian, Aravind, Chung, Raymond T., Straub, Beate K., Schuppan, Detlef, Ankavay, Maliki, Cocquerel, Laurence, Schaeffer, Evelyne, Goossens, Nicolas, Koh, Anna P., Mahajan, Milind, Nair, Venugopalan D., Gunasekaran, Ganesh, Schwartz, Myron E., Bardeesy, Nabeel, Shalek, Alex K., Rozenblatt-Rosen, Orit, Regev, Aviv, Felli, Emanuele, Pessaux, Patrick, Tanabe, Kenneth K., Heikenwälder, Mathias, Schuster, Catherine, Pochet, Nathalie, Zeisel, Mirjam B., Fuchs, Bryan C., Hoshida, Yujin, Baumert, Thomas F., Institut de Recherche sur les Maladies Virales et Hépatiques (IVH), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Texas Southwestern Medical Center [Dallas], Massachusetts General Hospital [Boston], Harvard Medical School [Boston] (HMS), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Universität Heidelberg [Heidelberg] = Heidelberg University, Nouvel Hôpital Civil de Strasbourg, University Hospital Basel [Basel], Hiroshima University, Icahn School of Medicine at Mount Sinai [New York] (MSSM), Kumamoto University, Broad Institute [Cambridge], Harvard University-Massachusetts Institute of Technology (MIT), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University (JGU), University Medical Center of the Johannes Gutenberg-University Mainz, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Immunopathologie et chimie thérapeutique (ICT), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Geneva University Hospital (HUG), Massachusetts Institute of Technology (MIT), Harvard University, This work was supported by ARC, Paris and Institut Hospitalo-Universitaire, Strasbourg (TheraHCC1.0 and 2.0 IHUARC IHU201301187 and IHUARC2019 to T.F.B.), the European Union (ERC-AdG-2014-671231-HEPCIR to T.F.B. and Y.H., EU H2020-667273-HEPCAR to T.F.B. and M.H., and INTERREG-IV-Rhin Supérieur-FEDER-Hepato-Regio-Net 2012 to T.F.B. and M.B.Z), ANRS, Paris (2013/108 and ECTZ103701 to T.F.B), NIH (DK099558 to Y. H., and CA233794 to Y.H. and T. F. B, CA140861 to B.C.F., and CA209940, R21CA209940, and R03AI131066 to N.P. and T.F.B.), Cancer Prevention and Research Institute of Texas (RR180016 to Y.H.), US Department of Defense (W81XWH-16-1-0363 to T.F.B. and Y.H.), the Irma T. Hirschl/Monique Weill-Caulier Trust (Y.H.), and the Foundation of the University of Strasbourg (HEPKIN to T. F. B. and Y. H.) and the Institut Universitaire de France (IUF, T.F.B.). M.H. is supported by an ERC CoG grant (HepatoMetaboPath) and EOS grant and by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)—Project-ID 272983813—TRR 179, and Project-ID 314905040 SFB TR209. This work has been published under the framework of the LABEX ANR-10-LABX-0028_HEPSYS and Inserm Plan Cancer and benefits from funding from the state managed by the French National Research Agency as part of the Investments for the future program., ANR-10-LABX-0028,HepSys,Functional genomics of viral hepatitis and liver disease(2010), European Project: 671231,H2020,ERC-2014-ADG,HEPCIR(2016), European Project: 667273,H2020,H2020-PHC-2015-two-stage,HEP-CAR(2016), Cocquerel, Laurence, Functional genomics of viral hepatitis and liver disease - - HepSys2010 - ANR-10-LABX-0028 - LABX - VALID, Cell circuits as targets and biomarkers for liver disease and cancer prevention - HEPCIR - - H20202016-01-01 - 2020-12-31 - 671231 - VALID, Mechanisms underlying hepatocellular carcinoma pathogenesis and impact of co-morbidities. - HEP-CAR - - H20202016-01-01 - 2019-12-31 - 667273 - VALID, Universität Heidelberg [Heidelberg], Harvard University [Cambridge]-Massachusetts Institute of Technology (MIT), Harvard University [Cambridge], Johannes Gutenberg - Universität Mainz (JGU), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, and Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)
Subjects: Liver Cirrhosis, Male, Carcinoma, Hepatocellular, Hepatocellular carcinoma, Carcinogenesis, Science, [SDV.CAN]Life Sciences [q-bio]/Cancer, Hepacivirus, Sciences du Vivant [q-bio]/Médecine humaine et pathologie, Chemoprevention, Models, Biological, Article, Cohort Studies, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cell Line, Tumor, Drug Discovery, Cancer genomics, Cyclic AMP, Animals, Humans, Cyclic AMP Response Element-Binding Protein, Immunologic Surveillance, Liver diseases, Nizatidine, Inflammation, Mice, Knockout, Macrophages, Liver Neoplasms, Prognosis, Hepatitis C, Computational biology and bioinformatics, Gene Expression Regulation, Neoplastic, Disease Models, Animal, Mechanisms of disease, HEK293 Cells, Liver, Hepatocytes, Transcriptome, Signal Transduction
Abstract: Chronic liver disease and hepatocellular carcinoma (HCC) are life-threatening diseases with limited treatment options. The lack of clinically relevant/tractable experimental models hampers therapeutic discovery. Here, we develop a simple and robust human liver cell-based system modeling a clinical prognostic liver signature (PLS) predicting long-term liver disease progression toward HCC. Using the PLS as a readout, followed by validation in nonalcoholic steatohepatitis/fibrosis/HCC animal models and patient-derived liver spheroids, we identify nizatidine, a histamine receptor H2 (HRH2) blocker, for treatment of advanced liver disease and HCC chemoprevention. Moreover, perturbation studies combined with single cell RNA-Seq analyses of patient liver tissues uncover hepatocytes and HRH2+, CLEC5Ahigh, MARCOlow liver macrophages as potential nizatidine targets. The PLS model combined with single cell RNA-Seq of patient tissues enables discovery of urgently needed targets and therapeutics for treatment of advanced liver disease and cancer prevention., Drug and target discovery for advanced liver disease are hampered by a lack of suitable models for clinical translation. Here the authors present a human liver cell-based system modeling a clinical prognostic signature allowing to propose nizatidine for treatment of advanced liver fibrosis and hepatocellular carcinoma prevention.
Published: 2021
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10. Case Report: Acquired Disseminated BCG in the Context of a Delayed Immune Reconstitution After Hematological Malignancy

Author: Vincent Gies, Yannick Dieudonné, Florence Morel, Wladimir Sougakoff, Raphaël Carapito, Aurélie Martin, Noëlle Weingertner, Léa Jacquel, Fabrice Hubele, Cornelia Kuhnert, Sophie Jung, Frederic Schramm, Pierre Boyer, Yves Hansmann, François Danion, Anne-Sophie Korganow, Aurélien Guffroy, Immuno-Rhumatologie Moléculaire, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA), Immunopathologie et chimie thérapeutique (ICT), Centre National de la Recherche Scientifique (CNRS)-Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), and Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, Candidate gene, Immunology, Context (language use), Disease, complex mixtures, 03 medical and health sciences, 0302 clinical medicine, Immune system, contamination, Immunity, BCGosis-susceptible PIDs, medicine, Immunology and Allergy, Immunodeficiency, case report, BCG, hematological malignancies, Mycobacterium bovis, biology, business.industry, RC581-607, medicine.disease, biology.organism_classification, 3. Good health, 030104 developmental biology, Immunologic diseases. Allergy, business, Complication, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030215 immunology
Abstract: ContextDisseminated infections due to Mycobacterium bovis Bacillus Calmette-Guérin (BCG) are unusual and occur mostly in patients with inborn error of immunity (IEI) or acquired immunodeficiency. However, cases of secondary BCGosis due to intravesical BCG instillation have been described. Herein, we present a case of severe BCGosis occurring in an unusual situation.Case DescriptionWe report one case of severe disseminated BCG disease occurring after hematological malignancy in a 48-year-old man without BCG instillation and previously vaccinated in infancy with no complication. Laboratory investigations demonstrated that he was not affected by any known or candidate gene of IEI or intrinsic cellular defect involving IFNγ pathway. Whole genome sequencing of the BCG strain showed that it was most closely related to the M. bovis BCG Tice strain, suggesting an unexpected relationship between the secondary immunodeficiency of the patient and the acquired BCG infection.ConclusionThis case highlights the fact that, in addition to the IEI, physicians, as well as microbiologists and pharmacists should be aware of possible acquired disseminated BCG disease in secondary immunocompromised patients treated in centers that administrate BCG for bladder cancers.
Published: 2021
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11. Hybrid Interfaces Made of Nanotubes and Backbone-Altered Dipeptides Tune Neuronal Network Architecture

Author: Bhimareddy Dinesh, Alberto Bianco, Federica Lareno Faccini, Laura Ballerini, Federica Quici, Denis Scaini, Manuela Medelin, Immunopathologie et chimie thérapeutique (ICT), Centre National de la Recherche Scientifique (CNRS)-Institut de biologie moléculaire et cellulaire (IBMC), and Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Imagination, Materials science, Chemical substance, Physiology, hippocampal neurons, Cognitive Neuroscience, media_common.quotation_subject, diphenylalanine, Biocompatible Materials, Nanotechnology, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Carbon nanotube, Conjugated system, carbon nanotubes, patch-clamp, peptides, self-assembly, Settore BIO/09 - Fisiologia, Hippocampus, Biochemistry, Nanomaterials, law.invention, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, law, Biological neural network, Animals, Diphenylalanine, 030304 developmental biology, media_common, Neurons, 0303 health sciences, Tissue Engineering, Nanotubes, Carbon, Cell Biology, General Medicine, Rats, chemistry, Chimie/Chimie thérapeutique, Self-assembly, Nerve Net, 030217 neurology & neurosurgery
Abstract: Peptides constituted of backbone homologated α-amino acids combined with carbon materials offer interesting possibilities in the modulation of cellular functions. In this work, we have prepared diphenylalanine β- and γ-peptides and conjugated them to carbon nanotubes (CNTs). These hybrids were able to self-assemble into fibrillar dendritic structures enabling the growth of primary hippocampal cells and the modulation of their neuronal functions. In particular, following the deposition of the different nanomaterials on glass substrates, we have evaluated their effects on circuit function and geometry. The geometrical restrictions due to CNT nucleated nodes allowed growth of neuronal networks with control over network geometry, and exploring its functional impact. In diverse applications from basic neuroscience, the presence of CNT nodes may be exploited in brain interfaces able to convey highly localized electrical stimuli.
Published: 2019
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12. A Flexible Method for Covalent Double Functionalization of Graphene Oxide

Author: Yuta Nishina, Alberto Bianco, Shi Guo, Cécilia Ménard-Moyon, Immunopathologie et chimie thérapeutique (ICT), Centre National de la Recherche Scientifique (CNRS)-Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), and Okayama University
Subjects: small ring systems, materials science, Aucun, Carbon materials, Oxide, Epoxide, surface chemistry, 02 engineering and technology, Conjugated system, Benzoquinone, 010402 general chemistry, 01 natural sciences, Catalysis, law.invention, chemistry.chemical_compound, law, Michael addition, Multifunctional materials, 010405 organic chemistry, Graphene, graphene, General Medicine, [CHIM.MATE]Chemical Sciences/Material chemistry, General Chemistry, 021001 nanoscience & nanotechnology, Combinatorial chemistry, 0104 chemical sciences, chemistry, Covalent bond, Epoxide ring opening, Michael reaction, Surface modification, 0210 nano-technology
Abstract: International audience; We have developed an easy method for the double functionalization of graphene oxide (GO) using benzoquinone in mild alkaline conditions. Two functional groups were covalently linked onto GO following two separate steps: the first group was attached by an epoxide ring opening reaction while the second moiety, bearing an amine function, was covalently conjugated through a Michael addition on benzoquinone covalently bound in turn to GO. The double functionalized GO was characterized by different techniques including FT-IR and X-ray photoelectron spectroscopy, thermogravimetric analysis, cyclic voltammetry, transmission electron microscopy, and atomic force microscopy confirming the sequential covalent modification of GO surface with two different functional groups. This method is straightforward and the conditions are mild, thus allowing to preserve the structure and properties of GO. This strategy could be exploited to prepare multifunctional GO conjugates with potential applications in many fields from materials science to biomedicine.
Published: 2019
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13. IKZF1 Loss-of-Function Variant Causes Autoimmunity and Severe Familial Antiphospholipid Syndrome

Author: Raphael Carapito, Yannick Dieudonné, Aurélien Guffroy, Anne-Sophie Korganow, Olivier Vollmer, Immunopathologie et chimie thérapeutique (ICT), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Immuno-Rhumatologie Moléculaire, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA)
Subjects: 0303 health sciences, medicine.medical_specialty, business.industry, Immunology, b-cells ikaros, medicine.disease_cause, Autoimmunity, 03 medical and health sciences, 0302 clinical medicine, Medical microbiology, medicine, Immunology and Allergy, business, Familial antiphospholipid syndrome, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Loss function, 030304 developmental biology, 030215 immunology
Published: 2019
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14. Selectins impair regulatory T cell function and contribute to systemic lupus erythematosus pathogenesis

Author: Pierre Duffau, Maya Saleh, Anne Garreau, Emmanuel Ribeiro, Isabelle Douchet, Lionel Couzi, Irène Machelart, Cécile Contin-Bordes, Marc Scherlinger, Patrick Blanco, Jean-Philippe Guegan, Vivien Guillotin, Thierry Schaeverbeke, Patrick Legembre, Marie-Elise Truchetet, Andrea Boizard-Moracchini, Agathe Vermorel, Nathalie Merillon, Jean-François Viallard, Estibaliz Lazaro, Vanja Sisirak, Christophe Richez, Thomas Barnetche, Pierre Vacher, Jean-Luc Pellegrin, Hélène Dumortier, Immunology from Concept and Experiments to Translation (ImmunoConcept), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Actions for OnCogenesis understanding and Target Identification in ONcology (ACTION), Institut Bergonié [Bordeaux], UNICANCER-UNICANCER-Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Immunopathologie et chimie thérapeutique (ICT), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), SISIRAK, VANJA, Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bordeaux Segalen - Bordeaux 2-Institut Bergonié [Bordeaux], UNICANCER-UNICANCER, Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), and Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, Regulatory T cell, [SDV]Life Sciences [q-bio], Syk, T-Lymphocytes, Regulatory, Mice, 03 medical and health sciences, 0302 clinical medicine, Transforming Growth Factor beta, Interferon, immune system diseases, medicine, Animals, Humans, Lupus Erythematosus, Systemic, skin and connective tissue diseases, Lupus erythematosus, biology, business.industry, General Medicine, Transforming growth factor beta, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], 030104 developmental biology, medicine.anatomical_structure, Immunology, Selectins, biology.protein, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Antibody, business, Selectin, 030215 immunology, Transforming growth factor, medicine.drug
Abstract: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by a loss of tolerance toward self-nucleic acids, autoantibody production, interferon expression and signaling, and a defect in the regulatory T (Treg) cell compartment. In this work, we identified that platelets from patients with active SLE preferentially interacted with Treg cells via the P-selectin/P-selectin glycoprotein ligand-1 (PSGL-1) axis. Selectin interaction with PSGL-1 blocked the regulatory and suppressive properties of Treg cells and particularly follicular Treg cells by triggering Syk phosphorylation and an increase in intracytosolic calcium. Mechanistically, P-selectin engagement on Treg cells induced a down-regulation of the transforming growth factor–β axis, altering the phenotype of Treg cells and limiting their immunosuppressive responses. In patients with SLE, we found an up-regulation of P- and E-selectin both on microparticles and in their soluble forms that correlated with disease activity. Last, blocking P-selectin in a mouse model of SLE improved cardinal features of the disease, such as anti-dsDNA antibody concentrations and kidney pathology. Overall, our results identify a P-selectin–dependent pathway that is active in patients with SLE and validate it as a potential therapeutic avenue.
Published: 2021
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15. A glutathione responsive nanoplatform made of reduced graphene oxide and MnO 2 nanoparticles for photothermal and chemodynamic combined therapy

Author: Ma, Baojin, Nishina, Yuta, Bianco, Alberto, Immunopathologie et chimie thérapeutique (ICT), Institut de biologie moléculaire et cellulaire (IBMC), and Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Fenton reaction, Cancer therapy, GSH depletion, Drug delivery, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Reactive oxygen species
Abstract: International audience; Based on the specific tumor microenvironment, characterized by an overproduction of H2O2 and a high glutathione (GSH) concentration, the cascade reactions of nanomaterials, capable of mediating GSH depletion and reactive oxygen species (ROS) generation, have become a popular strategy to increase cancer therapy efficiency. In this study, we exploited reduced graphene oxide (rGO), one of the most promising graphene-based materials, in combination with manganese dioxide nanoparticles (MnO2 NPs) to design a multifunctional nanoplatform (rGO@MnO2) for efficient photothermal/chemodynamic combined therapies. MnO2 NPs were anchored onto the surface of rGO nanosheets (rGO NSs). MnO2 NPs oxidize intracellular GSH, and the generated Mn 2+ ions converted H2O2 into HO by Fenton reaction. Meanwhile, rGO NSs mediated photothermal therapy (PTT) could further kill cancer cells. High temperature caused by photothermal conversion increased Fenton reaction rate, which enhanced the efficiency of MnO2 NPs mediated chemodynamic therapy (CDT). Importantly, thanks to the enhanced cell uptake of MnO2 NPs favored by the delivery properties of rGO, rGO@MnO2 possessed higher lethality to cancer cells. The decrease in the nanomaterials' effective dose would further improve biosecurity and reduce cost. Therefore, rGO@MnO2 have great potential in cancer therapy by exploiting the synergistic effect of PTT and photothermal/delivery effect enhanced CDT.
Published: 2021

16. Granulomatous manifestations associated with COVID19 infection: Is there a link between these two diseases?

Author: Aurélien Guffroy, Anne Sophie Korganow, Jean-Christophe Weber, M. Rondeau-Lutz, Juliette Jeannel, Philippe Mertz, S. Lescuyer, Immunopathologie et chimie thérapeutique (ICT), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de recherches interdisciplinaires sur les sciences et la technologie (IRIST), Université de Strasbourg (UNISTRA), Archives Henri-Poincaré - Philosophie et Recherches sur les Sciences et les Technologies (AHP-PReST), Université de Strasbourg (UNISTRA)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Histoire des Sciences et de Philosophie - Archives Henri Poincaré (LHSP), and Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Mucosal associated invariant T cells, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Sarcoidosis, COVID19, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Immunology, Mucosal associated invariant T cell, Peptidyl-Dipeptidase A, Article, Angiotensin-converting enzyme II, 03 medical and health sciences, 0302 clinical medicine, medicine, Immunology and Allergy, Humans, 030304 developmental biology, 0303 health sciences, Granulomatous disease, business.industry, SARS-CoV-2, COVID-19, medicine.disease, Virology, 030220 oncology & carcinogenesis, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Published: 2021
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17. Follow-up of COVID-19 patients: LA is transient but other aPLs are persistent

Author: Olivier Collange, Benoit Nespola, Charlotte Kaeuffer, Aurélien Guffroy, Thierry Martin, Yves Hansmann, Mirjana Radosavljevic, Paul-Michel Mertes, Anne-Sophie Korganow, Charles-Ambroise Tacquard, Yannick Dieudonné, Laurent Sattler, Xavier Delabranche, Olivier Morel, Vincent Poindron, Olivier Vollmer, Lelia Grunebaum, Vincent Gies, Laurent Arnaud, Jean-Christophe Weber, Mitochondrie, stress oxydant et protection musculaire (MSP), Université de Strasbourg (UNISTRA), Immunopathologie et chimie thérapeutique (ICT), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Virulence bactérienne précoce : fonctions cellulaires et contrôle de l'infection aiguë et subaiguë, Archives Henri-Poincaré - Philosophie et Recherches sur les Sciences et les Technologies (AHP-PReST), Université de Strasbourg (UNISTRA)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Histoire des Sciences et de Philosophie - Archives Henri Poincaré (LHSP), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Nanomédecine Régénérative (NanoRegMed), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immuno-Rhumatologie Moléculaire, and Stress vasculaire et tissulaire en transplantation : microparticules et environnement
Subjects: 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Anti-phospholipid antibodies, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Immunology, 030204 cardiovascular system & hematology, Sciences du Vivant [q-bio]/Médecine humaine et pathologie, Article, Lupus Coagulation Inhibitor, 03 medical and health sciences, 0302 clinical medicine, Antiphospholipid syndrome, Humans, Immunology and Allergy, Medicine, 030304 developmental biology, 0303 health sciences, Lupus anticoagulant, SARS-CoV-2, business.industry, Follow up studies, COVID-19, Thrombosis, Antiphospholipid Syndrome, medicine.disease, Antibodies, Anticardiolipin, Antibodies, Antiphospholipid, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, APS, Follow-Up Studies
Published: 2021
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18. Tenascin‐C immobilizes infiltrating T lymphocytes through CXCL12 promoting breast cancer progression

Author: Murdamoothoo, Devadarssen, Sun, Zhen, Yilmaz, Alev, Riegel, Gilles, Abou-Faycal, Chérine, Deligne, Claire, Velazquez-Quesada, Ines, Erne, William, Nascimento, Marine, Morgelin, Matthias, Cremel, Gerard, Paul, Nicodème, Carapito, Raphaël, Veber, Romain, Dumortier, Hélène, Yuan, Jingping, Midwood, Kim, Loustau, Thomas, Orend, Gertraud, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Oxford [Oxford], Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Wuhan University [China], Tongji Medical College [HUST], Huazhong University of Science and Technology [Wuhan] (HUST), Biopathologie de la Myéline, Neuroprotection et Stratégies Thérapeutiques (BMNST), Immunopathologie et chimie thérapeutique (ICT), Centre National de la Recherche Scientifique (CNRS)-Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), and Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Medicine (General), animal structures, Tumor immune microenvironment, extracellular matrix, Immunology, [SDV.CAN]Life Sciences [q-bio]/Cancer, chemical and pharmacologic phenomena, CD8-Positive T-Lymphocytes, QH426-470, Article, Lymphocytes, Tumor-Infiltrating, R5-920, Neoplasms, Genetics, Humans, Cancer, Tenascin, hemic and immune systems, Articles, CXCL12, musculoskeletal system, Chemokine CXCL12, tenascin‐C, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, cd8 tumor infiltrating lymphocytes cxcl12 extracellular matrix tenascin c tumor immune microenvironment extracellular-matrix protein immune cells cxcr4 microenvironment classification immunotherapy tumorigenesis fibronectin activation chemotaxis, embryonic structures, tenascin-C, CD8 tumor infiltrating lymphocytes
Abstract: Immune checkpoint therapy, where CD8 tumor infiltrating T lymphocytes (TIL) are reactivated, is a promising anti‐cancer treatment approach, yet with low response rates. The extracellular matrix, in particular tenascin‐C, may generate barriers for TIL. To investigate this possibility, we used a MMTV‐NeuNT and syngeneic mammary gland grafting model derived thereof with engineered tenascin‐C levels and observed accumulation of CD8 TIL in tenascin‐C‐rich stroma. Inhibition studies revealed that tenascin‐C induced CXCL12 through TLR4. By binding CXCL12, tenascin‐C retained CD8 TIL in the stroma. Blockade of CXCR4, the receptor of CXCL12, enhanced macrophage and CD8 TIL infiltration and reduced tumor growth and subsequent metastasis. Retention of CD8 TIL by tenascin‐C/CXCL12 was also observed in human breast cancer by tissue staining. Moreover, whereas high CD8 TIL numbers correlated with longer metastasis‐free survival, this was not the case when also tenascin‐C and CXCL12 levels were high. Altogether, these results may be useful for improving tumor immunity as diagnostic tool and to formulate a future “TIL‐matrix‐release‐and‐reactivate” strategy., Matrix molecule Tenascin‐C influences immune exclusion by retaining CD8 TILs in the stroma. The release of CD8 TILs from the matrix restores immune defense, resulting in reduced tumor growth and subsequent metastasis of human breast cancer.
Published: 2021
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19. Developmental partitioning of SYK and ZAP70 prevents autoimmunity and cancer

Author: Zhengshan Chen, Maike Buchner, Kadriye Nehir Cosgun, Pauline Soulas-Sprauel, Nora Heisterkamp, Veronika Ecker, Lars Klemm, Anne Marie Knapp, Joo Y. Song, Friedemann Kiefer, Supraja Saravanakumar, Markus Müschen, Thierry Martin, Mark Robinson, Hassan Jumaa, Vu N. Ngo, Dana Ghergus, Tanya Siddiqi, Kohei Kume, Laura Oksa, Mickaël Martin, Teresa Sadras, Jevon Cutler, Lili Wang, Janet Winchester, Eric Meffre, Gal Lenz, Wing C. Chan, Jürgen Ruland, Akhilesh Pandey, Immunopathologie et chimie thérapeutique (ICT), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Tampere University, and Clinical Medicine
Subjects: Lymphoma, B-Cell, Chronic lymphocytic leukemia, B-cell receptor, Antigens, CD19, Syk, Receptors, Antigen, B-Cell, Autoimmunity, Biology, Article, 03 medical and health sciences, Negative selection, Mice, Phosphatidylinositol 3-Kinases, 0302 clinical medicine, Neoplasms, medicine, Immune Tolerance, Animals, Humans, Syk Kinase, Molecular Biology, B cell, 030304 developmental biology, 0303 health sciences, B-Lymphocytes, ZAP-70 Protein-Tyrosine Kinase, Models, Genetic, NFATC Transcription Factors, ZAP70, B cell selection, breakpoint cluster region, Cell Differentiation, Cell Biology, medicine.disease, Neoplasm Proteins, Enzyme Activation, medicine.anatomical_structure, Cell Transformation, Neoplastic, Cancer research, Calcium, 3111 Biomedicine, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Protein Binding, Signal Transduction
Abstract: Even though SYK and ZAP70 kinases share high sequence homology and serve analogous functions, their expression in B and T cells is strictly segregated throughout evolution. Here, we identified aberrant ZAP70 expression as a common feature in a broad range of B cell malignancies. We validated SYK as the kinase that sets the thresholds for negative selection of autoreactive and premalignant clones. When aberrantly expressed in B cells, ZAP70 competes with SYK at the BCR signalosome and redirects SYK from negative selection to tonic PI3K signaling, thereby promoting B cell survival. In genetic mouse models for B-ALL and B-CLL, conditional expression of Zap70 accelerated disease onset, while genetic deletion impaired malignant transformation. Inducible activation of Zap70 during B cell development compromised negative selection of autoreactive B cells, resulting in pervasive autoantibody production. Strict segregation of the two kinases is critical for normal B cell selection and represents a central safeguard against the development of autoimmune disease and B cell malignancies. acceptedVersion
Published: 2021
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20. Prevalence of antineutrophil cytoplasmic antibody (ANCA)‐associated vasculitis and spatial association with quarries in a French Northeast region

Author: Giorgiutti, Stéphane, Dieudonné, Yannick, Hinschberger, Olivier, Nespola, Benoît, Campagne, Julien, Rakotoarivelo, Hanta Nirina, Hannedouch, Thierry, Moulin, Bruno, Blaison, Gilles, Weber, Jean-Christophe, Dalmas, Marie‐Caroline, De Blay De Gaix, Frederic, Lipsker, Dan, Chantrel, François, Gottenberg, Jacques Eric, Dimitrov, Yves, Imhoff, Olivier, Gavand, Pierre‐Edouard, Andres, Emmanuel, Debry, Christian, Hansmann, Yves, Klein, Alexandre, Lohmann, Caroline, Mathiaux, François, Guffroy, Aurélien, Poindron, Vincent, Martin, Thierry, Korganow, Anne-sophie, Arnaud, Laurent, Immunopathologie et chimie thérapeutique (ICT), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Archives Henri-Poincaré - Philosophie et Recherches sur les Sciences et les Technologies (AHP-PReST), Université de Strasbourg (UNISTRA)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Histoire des Sciences et de Philosophie - Archives Henri Poincaré (LHSP), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Mitochondrie, stress oxydant et protection musculaire (MSP), Université de Strasbourg (UNISTRA), Biomatériaux et Bioingénierie (BB), Université de Strasbourg (UNISTRA)-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Virulence bactérienne précoce : fonctions cellulaires et contrôle de l'infection aiguë et subaiguë, Immuno-Rhumatologie Moléculaire, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA)
Subjects: [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Objective: Silica is one of the strongest environmental substances linked with autoimmunity. The aim of this study was to assess the prevalence of granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and renal limited vasculitis (RLV) in a French northeast region, and their geospatial association with quarries. Methods: Potential ANCA-Associated Vasculitis (AAV) cases were identified using three sources: hospital records, immunology laboratories and the National Health Insurance System. Patients who resided in Alsace on January 1, 2016 and fulfilled ACR AAV criteria or Chapel Hill Consensus Conference 2012 definition were included. Incomplete case ascertainment was corrected using capture-recapture analysis. The spatial association between the number of cases and quarries in each administrative entity was assessed using geographical weighted regression (GWR). Results: From 910 potential AAV cases, we identified 185 patients meeting inclusion criteria: 120 GPA, 35 MPA, 30 RLV. The number of cases missed by any source was 6.4 (95%CI 3.6-11.5). Accordingly, the 2016 estimated prevalence in Alsace was 65.5 cases per million inhabitants (95%CI 47.3-93.0) for GPA, 19.1 (95%CI 11.3-34.3) for MPA, and 16.8 (95%CI 8.7-35.2) for RLV. The risk of AAV was significantly increased in communes with quarries (OR: 2.51 [95%CI: 1.66-3.80]) and GWR revealed a significant spatial association between quarries and GPA cases (p = 0.039), and, regarding ANCA serotype, between quarries and both PR3-AAV (p = 0.04) and MPO-AAV (p = 0.03)." Conclusion: In a region with a high density of quarries, the spatial association of AAV with quarries supports the role of silica as a specific environmental factor.
Published: 2021
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21. Biodegradation of graphene materials catalyzed by human eosinophil peroxidase

Author: Cristina Martín, Alberto Bianco, Yuta Nishina, Rajendra Kurapati, Vincenzo Palermo, Immunopathologie et chimie thérapeutique (ICT), Institut de biologie moléculaire et cellulaire (IBMC), and Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Eosinophil Peroxidase, Oxide, 02 engineering and technology, Spectrum Analysis, Raman, 010402 general chemistry, 01 natural sciences, Catalysis, law.invention, chemistry.chemical_compound, law, Oxidative enzyme, Humans, Physical and Theoretical Chemistry, Hydrogen peroxide, chemistry.chemical_classification, biology, Chemistry, Graphene, [CHIM.MATE]Chemical Sciences/Material chemistry, Biodegradation, 021001 nanoscience & nanotechnology, Combinatorial chemistry, Nanostructures, 0104 chemical sciences, Enzyme, biology.protein, Graphite, Chimie/Chimie thérapeutique, 0210 nano-technology, Eosinophil peroxidase
Abstract: International audience; Understanding the biodegradability of graphene materials by the action of oxidative enzymes secreted by the immune cells is essential for developing applicable biomedical products based on graphene materials. Herein, we demonstrate the biodegradation of graphene oxide (GO) by recombinant eosinophil peroxidase (EPO) enzyme extracted from human eosinophils in the presence of a low concentration of hydrogen peroxide and NaBr. We compared the degradation capability of the enzyme on three different GO samples containing different degrees of oxygen functional groups on their graphenic lattices. EPO succeeded in degrading the three tested GO samples within 90 h treatment. Raman spectroscopy and transmission electron microscopy analyses provided clear-cut evidence for biodegradation of GO by EPO catalysis. Our results provide more insights into a better understanding of biodegradation of graphene materials, helping to the design of future biomedical products based on these carbon nanomaterials.
Published: 2021
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22. How macrophages respond to two-dimensional materials: a critical overview focusing on toxicity

Author: Zhengmei Song, Alberto Bianco, Hazel Lin, Immunopathologie et chimie thérapeutique (ICT), Institut de biologie moléculaire et cellulaire (IBMC), and Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: tungsten, medicine.medical_treatment, Activation markers, Nanotechnology, Inflammation, 02 engineering and technology, 010402 general chemistry, 01 natural sciences, Nanomaterials, law.invention, molybdenum, Immune system, law, Quantum Dots, medicine, Animals, Humans, nanomaterials, Potential impact, Chemistry, Graphene, Macrophages, Immune cells, graphene, Phosphorus, [CHIM.MATE]Chemical Sciences/Material chemistry, General Medicine, 2D materials, 021001 nanoscience & nanotechnology, Pollution, 0104 chemical sciences, Nanostructures, Cytokine, Toxicity, manganese, Cytokines, Graphite, Chimie/Chimie thérapeutique, medicine.symptom, boron, 0210 nano-technology, Food Science
Abstract: International audience; With wider use of graphene-based materials and other two-dimensional (2D) materials in various fields, including electronics, composites, biomedicine, etc., 2D materials can trigger undesired effects at cellular, tissue and organ level. Macrophages can be found in many organs. They are one of the most important cells in the immune system and they are relevant in the study of nanomaterials as they phagocytose them. Nanomaterials have multi-faceted effects on phagocytic immune cells like macrophages, showing signs of inflammation in the form of pro-inflammatory cytokine or reactive oxidation species production, or upregulation of activation markers due to the presence of these foreign bodies. This review is catered to researchers interested in the potential impact and toxicity of 2D materials, particularly in macrophages, focusing on few-layer graphene, graphene oxide, graphene quantum dots, as well as other promising 2D materials containing molybdenum, manganese, boron, phosphorus and tungsten. We describe applications relevant to the growing area of 2D materials research, and the possible risks of ions and molecules used in the production of these promising 2D materials, or those produced by the degradation and dissolution of 2D materials.
Published: 2021

23. Gadolinium-Incorporated Carbon Nanodots for T 1 -Weighted Magnetic Resonance Imaging

Author: Da Zhang, Belén Ballesteros, Hanyu Liang, Giacomo Reina, Juan Li, Shi Guo, Alberto Bianco, Ding-Kun Ji, Cécilia Ménard-Moyon, Centre National de la Recherche Scientifique (France), Ministerio de Economía y Competitividad (España), Generalitat de Catalunya, Immunopathologie et chimie thérapeutique (ICT), Institut de biologie moléculaire et cellulaire (IBMC), and Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Fluorescence-lifetime imaging microscopy, Materials science, Gadolinium, chemistry.chemical_element, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Fluorescence, Contrast agents, Fluorescence imaging, Nuclear magnetic resonance, Magnetic resonance imaging, Carbon nanodots, T1 weighted, medicine, General Materials Science, Carbon nanomaterials, ComputingMilieux_MISCELLANEOUS, medicine.diagnostic_test, Toxicity, equipment and supplies, Theranostics, chemistry, Nanoparticles, Chemical stability, Chimie/Chimie thérapeutique, Graphene, human activities
Abstract: The design and development of contrast agents for magnetic resonance imaging (MRI) with improved chemical stability and higher contrasting capability for clinical translation compared to conventional contrast agents are still of great interest. In this study, a facile and universal approach was explored for controllable functionalization of red-emissive carbon nanodots (RCNDs) with diethylenetriaminepentaacetic anhydride (DTPA) for chelation of gadolinium. A series of accurate characterizations were used to control each step of the synthesis. The functionalization did not alter the band gap of the carbon nanodots, preserving their inherent far-red fluorescence. The as-prepared RCND-DTPA-Gd displayed a high colloidal stability with negligible Gd leakage. The nanodots also showed a better magnetic resonance relaxivity than commercial MRI agents. RCND-DTPA-Gd had good biocompatibility in vivo even at high doses. The systemically injected RCND-DTPA-Gd were found to be efficiently excreted through the renal route, a feature that further minimizes the potential toxicity risks. All these properties suggest that carbon nanodots can be well designed as efficient carriers of Gd, resulting in potential clinical tools as dual MRI/fluorescence functional probes for imaging applications. The approach described here could pave the pathway to a flexible strategy for the controllable functionalization of small-sized nanoparticles including carbon dots, rendering them more versatile. This work is expected to promote the future translation of carbon nanodots into clinical trials., We gratefully acknowledge the Centre National de la Recherche Scientifique (CNRS) and International Center for Frontier Research in Chemistry (icFRC), and financial support from the Agence Nationale de la Recherche (ANR) through the LabEx project Chemistry of Complex Systems (ANR-10-LABX-0026_CSC) within the Investissement d’Avenir program (ANR-10-120 IDEX-0002-02). We wish to thank D. Lamon for injecting the mice and collecting the samples for the biochemical analyses, C. Royer and V. Demais for help with TEM analyses at the “Plateforme Imagerie in vitro” at the Center of Neurochemistry (INCI, Strasbourg, France), D. Ihiawakrim for HRTEM measurements, and S. Guo for his help in the XPS analyses. ICN2 acknowledges the financial support from the Spanish Ministry of Economy and Competitiveness through the “Severo Ochoa” Programme for Centres of Excellence in R&D (SEV-2017-0706). B.B. acknowledges funding from Generalitat de Catalunya 2017 SGR 327. We wish to thank the Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fujian Key Laboratory of Integrative Medicine on Geriatrics, and Prof. Jun Peng for the use of 7 T small-animal MRI scanner.
Published: 2021
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24. Lateral dimension and amino-functionalization on the balance to assess the single-cell toxicity of graphene on fifteen immune cell types

Author: Vincenzo Palermo, Valentina Bordoni, Giacomo Reina, Açelya Yilmazer, Federica Collino, Cansu Gurcan, Claudia Fuoco, Shi Guo, Marco Orecchioni, Lucia Gemma Delogu, Barbara Zavan, Alberto Bianco, Martina Zoccheddu, Emanuele Treossi, Laura Fusco, Universita degli Studi di Padova, Università degli Studi di Sassari [Sassari] (UNISS), Institut de Science et d'ingénierie supramoléculaires (ISIS), Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Università degli Studi di Roma Tor Vergata [Roma], Ankara Üniversitesi, University of Sassari, University of Padua [Italy], Università degli Studi di Milano [Milano] (UNIMI), Università degli Studi di Ferrara (UniFE), University Hospital of Ferrara and Maria Cecilia Hospital, Istituto per la Sintesi Organica e la Fotoreattività - ISOF (Bologne, Italie), Consiglio Nazionale delle Ricerche [Bologna] (CNR), Immunopathologie et chimie thérapeutique (ICT), Institut de biologie moléculaire et cellulaire (IBMC), and Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: safety, Cell type, Biocompatibility, Materials Science (miscellaneous), 02 engineering and technology, 010501 environmental sciences, 2D materials, Carbon materials, Cytotoxicity, Safety, Single-cell, 01 natural sciences, Peripheral blood mononuclear cell, Monocytes, law.invention, Immune system, biocompatibility, law, medicine, Humans, Mass cytometry, Safety, Risk, Reliability and Quality, 0105 earth and related environmental sciences, carbon materials, Chemistry, Graphene, Monocyte, Settore MED/46 - Scienze Tecniche di Medicina di Laboratorio, Public Health, Environmental and Occupational Health, [CHIM.MATE]Chemical Sciences/Material chemistry, single-cell, 021001 nanoscience & nanotechnology, Cell biology, Nanostructures, medicine.anatomical_structure, Nanotoxicology, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Leukocytes, Mononuclear, cytotoxicity, Graphite, Chimie/Chimie thérapeutique, Single-Cell Analysis, 0210 nano-technology, Safety Research
Abstract: International audience; Given the wide variety of potential applications of graphene oxide (GO), its consequent release into the environment poses serious concerns on its safety. The future production and exploitation of graphene in the years to come should be guided by its specific chemical-physical characteristics. The unparalleled potential of single-cell mass cytometry (CyTOF) to dissect by high-dimensionality the specific immunological effects of nanomaterials, represents a turning point in nanotoxicology. It helps us to identify the safe graphene in terms of physical-chemical properties and therefore to direct its future safe production.Here we present a high-dimensional study to evaluate two historically indicated as key parameters for the safe exploitation: functionalization and dimension. The role of lateral dimension and the amino-functionalization of GO on their immune impact were here evaluated as synergistic players. To this end, we dissected the effects of GO, characterized by a large or small lateral size (GO 1.32 μm and GO 0.13 μm, respectively), and its amino-functionalized counterpart (GONH2 1.32 μm and GONH2 0.13 μm, respectively) on fifteen cell types of human primary peripheral blood mononuclear cells (PBMCs).We describe how the smallest later size not only evokes pronounced toxicity on the pool of PBMCs compared to larger GOs but also towards the distinct immune cell subpopulations, in particular on non-classical monocytes, plasmacytoid dendritic cells (pDCs), natural killer cells (NKs) and B cells. The amino-functionalization was able to improve the biocompatibility of classical and non-classical monocytes, pDCs, NKs, and B cells. Detailed single-cell analysis further revealed a complex interaction of all GOs with the immune cells, and in particular monocyte subpopulations, with different potency depending on their physicochemical properties. Overall, by high-dimensional profiling, our study demonstrates that the lateral dimension is an important factor modulating immune cells and specifically monocyte activation, but a proper surface functionalization is the dominant characteristic in its immune effects. In particular, the amino-functionalization can critically modify graphene impact dampening the immune cell activation. Our study can serve as a guide for the future broad production and use of graphene in our everyday life.
Published: 2021
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25. Graphene: A Disruptive Opportunity for COVID‐19 and Future Pandemics?

Author: Giacomo Reina, Alberto Bianco, Paolo Samorì, Daniel Iglesias, Immunopathologie et chimie thérapeutique (ICT), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut de Science et d'ingénierie supramoléculaires (ISIS), Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Université de Strasbourg (UNISTRA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Université Louis Pasteur - Strasbourg I-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and univOAK, Archive ouverte
Subjects: 2019-20 coronavirus outbreak, Materials science, Coronavirus disease 2019 (COVID-19), Surface Properties, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Nanotechnology, 02 engineering and technology, Biosensing Techniques, 010402 general chemistry, 01 natural sciences, Antiviral Agents, antimicrobials, SARS‐CoV‐2, law.invention, Viral Proteins, law, Limit of Detection, Active component, Pandemic, Humans, General Materials Science, Biomedical technology, Electrodes, sensing, carbon nanomaterials, [CHIM.MATE] Chemical Sciences/Material chemistry, Graphene, SARS-CoV-2, Mechanical Engineering, Chimie/Matériaux, COVID-19, [CHIM.MATE]Chemical Sciences/Material chemistry, Electrochemical Techniques, 021001 nanoscience & nanotechnology, 2D materials, 0104 chemical sciences, 3. Good health, Nanostructures, Mechanics of Materials, Paradigm shift, Perspective, Graphite, 0210 nano-technology, Antibodies, Immobilized
Abstract: The graphene revolution, which has taken place during the last 15 years, has represented a paradigm shift for science. The extraordinary properties possessed by this unique material have paved the road to a number of applications in materials science, optoelectronics, energy, and sensing. Graphene‐related materials (GRMs) are now produced in large scale and have found niche applications also in the biomedical technologies, defining new standards for drug delivery and biosensing. Such advances position GRMs as novel tools to fight against the current COVID‐19 and future pandemics. In this regard, GRMs can play a major role in sensing, as an active component in antiviral surfaces or in virucidal formulations. Herein, the most promising strategies reported in the literature on the use of GRM‐based materials against the COVID‐19 pandemic and other types of viruses are showcased, with a strong focus on the impact of functionalization, deposition techniques, and integration into devices and surface coatings., The present pandemic has motivated researchers with different backgrounds to fight against SARS‐CoV‐2. Graphene‐related materials present numerous benefits for new antiviral solutions. The interaction of graphene‐related materials with viruses, their virucidal activity, and their possible use in antiviral coatings and sensing devices for fast and reliable detection are highlighted.
Published: 2021
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26. The 'French Germinal Center Club' of the French Society for Immunology

Author: Ame, Patricia, Dumortier, Helene, Espeli, Marion, Milpied, Pierre, Fazilleau, Nicolas, Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Immunopathologie et chimie thérapeutique (ICT), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Ecotaxie, microenvironnement et développement lymphocytaire (EMily (UMR_S_1160 / U1160)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Chard-Hutchinson, Xavier
Subjects: [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio]
Abstract: International audience; The antibody response and B cell memory development are major effector arms of the immune system. They both rely on the selection of B cells in specific anatomical structures called germinal centers (GC). GCs are not only sites for clonal B cell expansion but also the places where the antibody repertoire diversifies following somatic hypermutations and class switch recombination. CD4+ T cells that are present in GCs guide the stringent cell selection of high-affinity B cell variants. They can be divided in two functional cell subsets: T follicular helper (Tfh) and T follicular regulatory (Tfr) cells. Furthermore, follicular B and T cell subsets are in close contact with specialized stromal cells allowing cell migration, adhesion, and participating in B cell selection mechanisms. Importantly, on top of their essential role as orchestrators of protective immune responses against infections, GCs have also been involved in diverse pathological conditions including autoimmunity, allergy, and cancer. The great complexity of these structures means that GC aficionados encompass researchers working on a very large palette of topics including in depth analysis of the immune cell types cited above, characterization of cell interactions between GC immune and/or mesenchymal cell subsets, as well as deciphering disease physiopathology. The great versatility of these research foci means that the GC field is extremely dynamic and multidisciplinary. However, because there are many scientific topics addressed when studying GC and despite a consequent number of teams interested in this field, events centered only on GCs allowing researcher interactions are quite rare.
Published: 2021
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27. The 'French Germinal Center Club' of the French Society for Immunology: a dynamic collaboration between researchers passionate about the germinal center reaction

Author: Hélène Dumortier, Marion Espéli, Patricia Amé, Pierre Milpied, Nicolas Fazilleau, Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Immunopathologie et chimie thérapeutique (ICT), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Ecotaxie, microenvironnement et développement lymphocytaire (EMily (UMR_S_1160 / U1160)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0303 health sciences, [SDV]Life Sciences [q-bio], Immunology, Library science, Germinal center, Biology, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Immunology and Allergy, Club, Intersectoral Collaboration, 030304 developmental biology, 030215 immunology
Abstract: International audience; The antibody response and B cell memory development are major effector arms of the immune system. They both rely on the selection of B cells in specific anatomical structures called germinal centers (GC). GCs are not only sites for clonal B cell expansion but also the places where the antibody repertoire diversifies following somatic hypermutations and class switch recombination. CD4+ T cells that are present in GCs guide the stringent cell selection of high-affinity B cell variants. They can be divided in two functional cell subsets: T follicular helper (Tfh) and T follicular regulatory (Tfr) cells. Furthermore, follicular B and T cell subsets are in close contact with specialized stromal cells allowing cell migration, adhesion, and participating in B cell selection mechanisms. Importantly, on top of their essential role as orchestrators of protective immune responses against infections, GCs have also been involved in diverse pathological conditions including autoimmunity, allergy, and cancer. The great complexity of these structures means that GC aficionados encompass researchers working on a very large palette of topics including in depth analysis of the immune cell types cited above, characterization of cell interactions between GC immune and/or mesenchymal cell subsets, as well as deciphering disease physiopathology. The great versatility of these research foci means that the GC field is extremely dynamic and multidisciplinary. However, because there are many scientific topics addressed when studying GC and despite a consequent number of teams interested in this field, events centered only on GCs allowing researcher interactions are quite rare.
Published: 2021
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28. The 'French Germinal Center Club' of the French Society for Immunology: a dynamic collaboration between researchers passionate about the germinal center reaction

Author: Ame, Patricia, Dumortier, Helene, Espeli, Marion, Milpied, Pierre, Fazilleau, Nicolas, Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Immunopathologie et chimie thérapeutique (ICT), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Ecotaxie, microenvironnement et développement lymphocytaire (EMily (UMR_S_1160 / U1160)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse III - Paul Sabatier (UT3), and Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SDV]Life Sciences [q-bio]
Abstract: International audience; The antibody response and B cell memory development are major effector arms of the immune system. They both rely on the selection of B cells in specific anatomical structures called germinal centers (GC). GCs are not only sites for clonal B cell expansion but also the places where the antibody repertoire diversifies following somatic hypermutations and class switch recombination. CD4+ T cells that are present in GCs guide the stringent cell selection of high-affinity B cell variants. They can be divided in two functional cell subsets: T follicular helper (Tfh) and T follicular regulatory (Tfr) cells. Furthermore, follicular B and T cell subsets are in close contact with specialized stromal cells allowing cell migration, adhesion, and participating in B cell selection mechanisms. Importantly, on top of their essential role as orchestrators of protective immune responses against infections, GCs have also been involved in diverse pathological conditions including autoimmunity, allergy, and cancer. The great complexity of these structures means that GC aficionados encompass researchers working on a very large palette of topics including in depth analysis of the immune cell types cited above, characterization of cell interactions between GC immune and/or mesenchymal cell subsets, as well as deciphering disease physiopathology. The great versatility of these research foci means that the GC field is extremely dynamic and multidisciplinary. However, because there are many scientific topics addressed when studying GC and despite a consequent number of teams interested in this field, events centered only on GCs allowing researcher interactions are quite rare.
Published: 2021
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29. 3-Dimensional graphene-like structures and applications: general discussion

Author: Girija Shankar Papanai, Harry Morgan, Alessandro Molle, Andrea C. Ferrari, Michele Melchionna, Vincenzo Palermo, Andrea Oyarzun, Christof Neumann, Claudia Backes, Ranjan Kumar Behera, Alejandro Criado, Stuart Goldie, Gang Wang, Maurizio Prato, Alberto Bianco, Zhenyuan Xia, Abigail Bellamy-Carter, Valérie Caps, Trevor Davies, Yuyoung Shin, Tim Nowack, Ruohong Sui, Cinzia Casiraghi, Stefano Fornasaro, Manuela Melucci, Wai Hin Lee, Vimal Kumar, Mark C. Hersam, Ali Reza Kamali, Vladimir Kolosov, Ivo F. Teixeira, Manish Chhowalla, Fernando Galembeck, Natalia Martsinovich, Immunopathologie et chimie thérapeutique (ICT), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut de chimie et procédés pour l'énergie, l'environnement et la santé (ICPEES), Université de Strasbourg (UNISTRA)-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Backes, C., Behera, R. K., Bellamy-Carter, A., Bianco, A., Caps, V., Casiraghi, C., Chhowalla, M., Criado, A., Davies, T., Ferrari, A. C., Fornasaro, S., Galembeck, F., Goldie, S., Hersam, M. C., Kamali, A. R., Kolosov, V., Kumar, V., Lee, W. H., Martsinovich, N., Melchionna, M., Melucci, M., Molle, A., Morgan, H., Neumann, C., Nowack, T., Oyarzun, A., Palermo, V., Papanai, G. S., Prato, M., Shin, Y., Sui, R., Teixeira, I. F., Wang, G., and Xia, Z.
Subjects: Computer science, Graphene, graphene, 2D materials, Nanotechnology, 02 engineering and technology, [CHIM.MATE]Chemical Sciences/Material chemistry, 010402 general chemistry, 021001 nanoscience & nanotechnology, 01 natural sciences, 0104 chemical sciences, law.invention, law, Physical and Theoretical Chemistry, 0210 nano-technology
Abstract: The first page of this article is displayed as the abstract.
Published: 2021
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30. Modélisation tridimensionnelle in vitro des systèmes nerveux et immunitaire de la peau

Author: Vincent Flacher, François Berthod, Quentin Muller, Université Laval [Québec] (ULaval), Immunologie et chimie thérapeutiques (ICT), Cancéropôle du Grand Est-Centre National de la Recherche Scientifique (CNRS), Immunopathologie et chimie thérapeutique (ICT), Institut de biologie moléculaire et cellulaire (IBMC), and Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, [SDV]Life Sciences [q-bio], Sensory system, General Medicine, Atopic dermatitis, Biology, medicine.disease, General Biochemistry, Genetics and Molecular Biology, In vitro, 3. Good health, Sensory function, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Immune system, Psoriasis, Skin structure, medicine, Neuroscience, 030217 neurology & neurosurgery
Abstract: Le système immunitaire et le système nerveux sensoriel sont responsables de la perception du danger, sous des formes distinctes mais complémentaires. Ces dernières années, les interactions neuro-immunes se sont imposées comme un axe de recherche important en dermatologie pour comprendre la cicatrisation, la dermatite atopique ou le psoriasis. Nous présentons ici une sélection de modèles tridimensionnels in vitro reproduisant la structure de la peau et intégrant une fonction immunitaire ou sensorielle. Les évolutions futures de ces modèles permettront d’obtenir une vision aussi complète que possible des influences réciproques entre système immunitaire et système nerveux sensoriel.
Published: 2021
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31. Refining 'Long-COVID' by a Prospective Multimodal Evaluation of Patients with Long-Term Symptoms Attributed to SARS-CoV-2 Infection

Author: Seiamak Bahram, Magali Perret, Jacques-Eric Gottenberg, Adrien Gras, Laurent Arnaud, Alexandre Belot, Renaud Felten, Luc Pijnenburg, Jean Sibilia, Sabrina Bibi-Triki, Sophie Trouillet-Assant, Raphael Carapito, Charlotte Nazon, Emmanuel Chatelus, Rachel Arnould-Michel, Floriane Gallais, Amaury C. Mengin, Pierre Vidailhet, Samira Fafi-Kremer, Marc Scherlinger, Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunopathologie et chimie thérapeutique (ICT), Centre National de la Recherche Scientifique (CNRS)-Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie moléculaire et cellulaire (IBMC), and Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Microbiology (medical), medicine.medical_specialty, Visual analogue scale, Pain, Physical examination, Serology, Patient perspective, 03 medical and health sciences, 0302 clinical medicine, Quality of life, Interquartile range, Internal medicine, Medicine, 030212 general & internal medicine, Prospective cohort study, Depression (differential diagnoses), Original Research, Disability, medicine.diagnostic_test, SARS-CoV-2, business.industry, Long-COVID, disability long-covid pain patient perspective sars-cov-2 consequences, 3. Good health, Infectious Diseases, Anxiety, medicine.symptom, business, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Introduction COVID-19 long-haulers, also decribed as having “long-COVID” or post-acute COVID-19 syndrome, represent 10% of COVID-19 patients and remain understudied. Methods In this prospective study, we recruited 30 consecutive patients seeking medical help for persistent symptoms (> 30 days) attributed to COVID-19. All reported a viral illness compatible with COVID-19. The patients underwent a multi-modal evaluation, including clinical, psychologic, virologic and specific immunologic assays and were followed longitudinally. A group of 17 convalescent COVID-19 individuals without persistent symptoms were included as a comparison group. Results The median age was 40 [interquartile range: 35–54] years and 18 (60%) were female. At a median time of 152 [102–164] days after symptom onset, fever, cough and dyspnea were less frequently reported compared with the initial presentation, but paresthesia and burning pain emerged in 18 (60%) and 13 (43%) patients, respectively. The clinical examination was unremarkable in all patients, although the median fatigue and pain visual analog scales were 7 [5–8] and 5 [2–6], respectively. Extensive biologic studies were unremarkable, and multiplex cytokines and ultra-sensitive interferon-α2 measurements were similar between long-haulers and convalescent COVID-19 individuals without persistent symptoms. Using SARS-CoV-2 serology and IFN-γ ELISPOT, we found evidence of a previous SARS-CoV-2 infection in 50% (15/30) of patients, with evidence of a lack of immune response, or a waning immune response, in two patients. Finally, psychiatric evaluation showed that 11 (36.7%), 13 (43.3%) and 9 (30%) patients had a positive screening for anxiety, depression and post-traumatic stress disorder, respectively. Conclusions Half of patients seeking medical help for post-acute COVID-19 syndrome lack SARS-CoV-2 immunity. The presence of SARS-CoV-2 immunity, or not, had no consequence on the clinical or biologic characteristics of post-acute COVID-19 syndrome patients, all of whom reported severe fatigue, altered quality of life and psychologic distress. Supplementary Information The online version contains supplementary material available at 10.1007/s40121-021-00484-w.
Published: 2021
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32. Current Clinical and Pre-Clinical Imaging Approaches to Study the Cancer-Associated Immune System

Author: Christopher G. Mueller, Christian Gaiddon, Aïna Venkatasamy, Immunopathologie et chimie thérapeutique (ICT), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Interface de Recherche Fondamentale et Appliquée en Cancérologie (IRFAC - Inserm U1113), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Paul Strauss : Centre Régional de Lutte contre le Cancer (CRLCC)-Fédération de Médecine Translationelle de Strasbourg (FMTS), L'Institut hospitalo-universitaire de Strasbourg (IHU Strasbourg), Institut National de Recherche en Informatique et en Automatique (Inria)-l'Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD)-Les Hôpitaux Universitaires de Strasbourg (HUS)-La Fédération des Crédits Mutuels Centre Est (FCMCE)-L'Association pour la Recherche contre le Cancer (ARC)-La société Karl STORZ, Gaiddon, Christian, Immunologie, Immunopathologie et Chimie Thérapeutique (I2CT), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), ANR-10-IDEX-0002,UNISTRA,Par-delà les frontières, l'Université de Strasbourg(2010), ANR-20-SFRI-0012,STRAT'US,Façonner les talents en formation et en recherche à l'Université de Strasbourg(2020), ANR-11-EQPX-0022,I2MC,Insectarium pour l'Infectiologie Moléculaire et Cellulaire(2011), ANR-20-CE93-0006,Lymphinnate,Analyse de l'interaction entre l'endothélium lymphatique et cellules immunitaires innées dans le ganglion lymphatique et son impact sur l'immunité adaptative(2020), ANR-19-CE14-0021,ANTIPODE,La spécificité tissulaire des effets paradoxaux de la thérapie anti-TNF dans les maladies inflammatoires de l'intestin(2019), ANR-10-IAHU-0002,MIX-Surg,Institut de Chirurgie Mini-Invasive guidée par l'Image(2010), Immunologie et chimie thérapeutiques (ICT), and Cancéropôle du Grand Est-Centre National de la Recherche Scientifique (CNRS)
Subjects: Diagnostic Imaging, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, [SDV]Life Sciences [q-bio], Mini Review, Immunology, Cancer therapy, [SDV.CAN]Life Sciences [q-bio]/Cancer, 02 engineering and technology, Cellular level, Sciences du Vivant [q-bio]/Cancer, Multimodal Imaging, Standard procedure, 03 medical and health sciences, Immune system, immune cells, [SDV.CAN] Life Sciences [q-bio]/Cancer, Neoplasms, Medicine, Immunology and Allergy, Animals, Humans, cancer, tertiary lymphoid structure, Clinical imaging, 030304 developmental biology, 0303 health sciences, business.industry, Non invasive, Cancer, imaging, RC581-607, lymph node, 021001 nanoscience & nanotechnology, medicine.disease, 3. Good health, Molecular Imaging, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, Risk analysis (engineering), [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, [SDV.IMM.IA] Life Sciences [q-bio]/Immunology/Adaptive immunology, Immune System, Lymphatic Metastasis, Lymph Nodes, Immunologic diseases. Allergy, 0210 nano-technology, business, Biomarkers
Abstract: In the light of the success and the expected growth of its arsenal, immuno-therapy may become the standard neoadjuvant procedure for many cancers in the near future. However, aspects such as the identity, organization and the activation status of the peri- and intra-tumoral immune cells would represent important elements to weigh in the decision for the appropriate treatment. While important progress in non-invasive imaging of immune cells has been made over the last decades, it falls yet short of entering the clinics, let alone becoming a standard procedure. Here, we provide an overview of the different intra-vital imaging approaches in the clinics and in pre-clinical settings and discuss their benefits and drawbacks for assessing the activity of the immune system, globally and on a cellular level. Stimulated by further research, the future is likely to see many technological advances both on signal detection and emission as well as image specificity and resolution to tackle current hurdles. We anticipate that the ability to precisely determine an immune stage of cancer will capture the attention of the oncologist and will create a change in paradigm for cancer therapy. journal article review research support, non-u.s. gov't 2021 2021 09 03 imported
Published: 2021
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33. Chikungunya Virus Envelope Protein E2 Provides a Vector for Targeted Antigen Delivery to Human Dermal CD14+ Dendritic Cells

Author: Olivier Chaloin, Christian Münz, Melanie Kraemer, Amandine Selle, Vincent Flacher, Marie Cumin, Astrid Hoste, Adrien Brulefert, Hans-Henrik Gad, Philippe Desprès, Christopher G. Mueller, Julia Rühl, Jean-Baptiste Madinier, Immunopathologie et chimie thérapeutique (ICT), Centre National de la Recherche Scientifique (CNRS)-Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Interactions Moléculaires Flavivirus-Hôtes, Institut Pasteur [Paris], Viral Immunobiology, Universität Zürich [Zürich] = University of Zurich (UZH)-Institute of Experimental Immunology [Zurich], Processus Infectieux en Milieu Insulaire Tropical (PIMIT), Centre National de la Recherche Scientifique (CNRS)-IRD-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de La Réunion (UR), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP), Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IRD-Centre National de la Recherche Scientifique (CNRS), University of Zurich, Flacher, Vincent, and FLACHER, Vincent
Subjects: 1303 Biochemistry, CD14, 610 Medicine & health, Dermatology, Biology, medicine.disease_cause, 10263 Institute of Experimental Immunology, Biochemistry, 2708 Dermatology, 1307 Cell Biology, 03 medical and health sciences, 0302 clinical medicine, Viral envelope, medicine, 1312 Molecular Biology, Vector (molecular biology), Chikungunya, Molecular Biology, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, Antigen delivery, Cell Biology, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, [SDV.MHEP.DERM] Life Sciences [q-bio]/Human health and pathology/Dermatology, Virology, 3. Good health, 030220 oncology & carcinogenesis, 570 Life sciences, biology, [SDV.IMM.IMM] Life Sciences [q-bio]/Immunology/Immunotherapy, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology
Abstract: International audience
Published: 2021
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34. B cells in primary antiphospholipid syndrome: Review and remaining challenges

Author: Vincent Poindron, Anne-Sophie Korganow, Yannick Dieudonné, Vincent Gies, Thierry Martin, Pauline Soulas Sprauel, Aurélien Guffroy, Immunopathologie et chimie thérapeutique (ICT), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Immuno-Rhumatologie Moléculaire, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA)
Subjects: 0301 basic medicine, Immunology, medicine.disease_cause, Autoimmunity, Autoimmune Diseases, 03 medical and health sciences, 0302 clinical medicine, Immune system, Antiphospholipid syndrome, Immunity, Immunology and Allergy, Medicine, Humans, B cell, 030203 arthritis & rheumatology, B-Lymphocytes, biology, business.industry, Autoantibody, medicine.disease, Antiphospholipid Syndrome, Phenotype, 3. Good health, 030104 developmental biology, medicine.anatomical_structure, biology.protein, Antibodies, Antiphospholipid, [SDV.IMM]Life Sciences [q-bio]/Immunology, Antibody, business
Abstract: It is now widely accepted that antiphospholipid antibodies (aPL) have direct pathogenic effects and that B cells, notably through aPL production, play a key role in the development of antiphospholipid syndrome (APS). Recent findings strengthened the implication of B cells with the description of specific B cell phenotype abnormalities and inborn errors of immunity involving B cell signaling in APS patients. In addition, it has been shown in preclinical models that cross-reactivity between APS autoantigens and mimotopes expressed by human gut commensals can lead to B cell tolerance breakdown and are sufficient for APS development. However, B cell targeting therapies are surprisingly not as effective as expected in APS compared to other autoimmune diseases. Elucidation of the B cell tolerance breakdown mechanisms in APS patients may help to develop and guide the use of novel therapeutic agents that target B cells or specific immune pathway.
Published: 2020
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35. Two-Dimensional Material-Based Biosensors for Virus Detection

Author: Kourosh Kalantar-zadeh, Alberto Bianco, Cécilia Ménard-Moyon, Immunopathologie et chimie thérapeutique (ICT), Institut de biologie moléculaire et cellulaire (IBMC), and Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Computer science, Aptamer, High selectivity, Bioengineering, 02 engineering and technology, Computational biology, Biosensing Techniques, 01 natural sciences, Virus, Nucleic Acids, Host organism, Humans, Instrumentation, Pandemics, Fluid Flow and Transfer Processes, Process Chemistry and Technology, Infection prevalence, 010401 analytical chemistry, [CHIM.MATE]Chemical Sciences/Material chemistry, 021001 nanoscience & nanotechnology, 0104 chemical sciences, 3. Good health, Virus detection, Virus Diseases, Viruses, Chimie/Chimie thérapeutique, 0210 nano-technology, Biosensor
Abstract: Viral infections are one of the major causes of mortality and economic losses worldwide. Consequently, efficient virus detection methods are crucial to determine the infection prevalence. However, most detection methods face challenges related to false-negative or false-positive results, long response times, high costs, and/or the need for specialized equipment and staff. Such issues can be overcome by access to low-cost and fast response point-of-care detection systems, and two-dimensional materials (2DMs) can play a critical role in this regard. Indeed, the unique and tunable physicochemical properties of 2DMs provide many advantages for developing biosensors for viral infections with high sensitivity and selectivity. Fast, accurate, and reliable detection, even at early infection stages by the virus, can be potentially enabled by highly accessible surface interactions between the 2DMs and the analytes. High selectivity can be obtained by functionalization of the 2DMs with antibodies, nucleic acids, proteins, peptides, or aptamers, allowing for specific binding to a particular virus, viral fingerprints, or proteins released by the host organism. Multiplexed detection and discrimination between different virus strains are also feasible. In this Review, we present a comprehensive overview of the major advances of 2DM-based biosensors for the detection of viruses. We describe the main factors governing the efficient interactions between viruses and 2DMs, making them ideal candidates for the detection of viral infections. We also critically detail their advantages and drawbacks, providing insights for the development of future biosensors for virus detection. Lastly, we provide suggestions to stimulate research in the fast expanding field of 2DMs that could help in designing advanced systems for preventing virus-related pandemics.
Published: 2020
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36. Osteoclasts contribute to early development of chronic inflammation by promoting dysregulated hematopoiesis and myeloid skewing

Author: Matthieu Rouleau, Thomas Ciucci, Henri-Jean Garchon, Claudine Blin-Wakkach, Abdelilah Wakkach, Julia Halper, Laurent Peyrin-Biroulet, Christopher G. Mueller, Maria-Bernadette Madel, Majlinda Topi, David Moulin, Lidia Ibáñez, Immunologie et chimie thérapeutiques (ICT), Cancéropôle du Grand Est-Centre National de la Recherche Scientifique (CNRS), Immunopathologie et chimie thérapeutique (ICT), Centre National de la Recherche Scientifique (CNRS)-Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de PhysioMédecine Moléculaire (LP2M), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), University of Rochester Medical Center (URMC), Infection et inflammation (2I), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), and Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)
Subjects: musculoskeletal diseases, 0303 health sciences, Myeloid, business.industry, [SDV]Life Sciences [q-bio], Hematopoietic stem cell, Inflammation, medicine.disease, 03 medical and health sciences, Haematopoiesis, 0302 clinical medicine, medicine.anatomical_structure, Osteoclast, 030220 oncology & carcinogenesis, medicine, Cancer research, In patient, Myelopoiesis, Colitis, medicine.symptom, business, 030304 developmental biology
Abstract: Increased myelopoiesis is a hallmark of many chronic inflammatory diseases. However, the mechanisms involved in the myeloid skewing of hematopoiesis upon inflammation are still incompletely understood. Here, we identify an unexpected role of bone-resorbing osteoclasts in promoting hematopoietic stem cell (HSC) proliferation and differentiation towards myeloipoiesis in the early phases of chronic colitis. RNAseq analysis revealed that osteoclasts in colitis differ from control ones and overexpress genes involved in the remodeling of HSC niches. We showed that colitic osteoclasts modulate the interaction of HSCs with their niche and promote myeloid differentiation. Increased osteoclast activity was correlated with an augmentation of myelopoiesis in patients with chronic colitis. Therapeutic blockade of osteoclasts reduced HSC proliferation and myeloid skewing and resulted in a decreased inflammation and severity of colitis. Together, these data identify osteoclasts as potent regulators of HSCs and promising target in chronic colitis.
Published: 2020
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37. SPHERE+: Imaging young Jupiters down to the snowline

Author: Augereau, J. -C., Baudino, J. -L., Beuzit, J. -L., Bouret, J. -C., Desert, J. -M., Delisle, J. -B., Orazi, V. D, Gonzalez, J. -F., Lagrange, A. -M., Coroller, H. Le, Arena, G. Muro, Diaye, M. N, Sauvage, J. -F., Schmid, H. -M., Boccaletti, A., Chauvin, G., Mouillet, D., Absil, O., Allard, F., Antoniucci, S., Augereau, J.-C, Barge, P., Baruffolo, A., Baudino, J.-L, Baudoz, P., Beaulieu, M., Benisty, M., Beuzit, J.-L, Bianco, A., Biller, B., Bonavita, B., Bonnefoy, M., Bos, S., Bouret, J.-C, Brandner, W., Buchschache, N., Carry, B., Cantalloube, F., Cascone, E., Carlotti, A., Charnay, B., Chiavassa, A., Choquet, E., Clenet, Y., Crida, A., De Boer, J., De Caprio, V., Desidera, S., Desert, J.-M, Delisle, J.-B, Delorme, P., Dohlen, K., Doelman, D., Dominik, C., D'orazi, V, Dougados, C., Douté, S., Fedele, D., Feldt, M., Ferreira, F., Fontanive, C., Fusco, T., Galicher, R., Garufi, A., Gendron, E., Ghedina, A., Ginski, C., Gonzalez, J.-F, Gratadour, D., Gratton, R., Guillot, T., Haffert, S., Hagelberg, J., Henning, T., Huby, E., Janson, M., Kamp, I., Keller, C. U., Kenworthy, M., Kervella, P., Kral, Q., Kuhn, J., Lagadec, E., Laibe, G., Langlois, M., Lagrange, A.-M, Launhardt, R., Leboulleux, L., Le Coroller, H, Causi, G. Li, Loupias, M., Maire, A. L., Marleau, G., Martinache, F., Martinez, P., Mary, D., Mattioli, M., Mazoyer, J., Meheut, H., Ménard, F., Mesa, D., Meunier, N., Miguel, Y., Milli, J., Min, M., Molliere, P., Mordasini, C., Moretto, G., Mugnier, L., Muro Arena, G, Nardetto, N., N'Diaye, M, Nesvadba, N., Pedichini, F., Pinilla, P., Por, E., Potier, A., Quanz, S., Rameau, J., Roelfsema, R., Rouan, D., Rigliaco, E., Salasnich, B., Samland, M., Sauvage, J.-F, Schmid, H.-M, Segransan, D., Snellen, I., Snik, F., Soulez, F., Stadler, E., Stam, D., Tallon, M., Thebault, P., Thiebaut, E., Tschudi, C., Udry, S., van Holstein, R., Vernazza, P, Vidal, F., Vigan, A., Waters, R., Wildi, F., Willson, M., Zanutta, A., Zavagno, Annie, Zurlo, A., Laboratoire d'Astrophysique de Marseille (LAM), Aix Marseille Université (AMU)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS), Leiden Observatory [Leiden], Universiteit Leiden [Leiden], Joseph Louis LAGRANGE (LAGRANGE), Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Observatoire de la Côte d'Azur, COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Observatoire de la Cte d’Azur, 96 Boulevard de l’Observatoire, Nice, 06300, France, Centre d'Etudes Lasers Intenses et Applications (CELIA), Université de Bordeaux (UB)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Observatoire de la Côte d'Azur, COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Département de Recherche sur la Fusion Contrôlée (DRFC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Jet Propulsion Laboratory (JPL), NASA-California Institute of Technology (CALTECH), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire de la Côte d'Azur, COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Institut de Planétologie et d'Astrophysique de Grenoble (IPAG), Centre National d'Études Spatiales [Toulouse] (CNES)-Observatoire des Sciences de l'Univers de Grenoble (OSUG ), Institut national des sciences de l'Univers (INSU - CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA)-Météo-France -Institut national des sciences de l'Univers (INSU - CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA)-Météo-France, Department of Biochemistry and Molecular Biology, Mayo Clinic, Astronomical Institute Anton Pannekoek (AI PANNEKOEK), University of Amsterdam [Amsterdam] (UvA), Physikalisches Institut [Bern], Universität Bern [Bern] (UNIBE), DOTA, ONERA, Université Paris Saclay [Châtillon], ONERA-Université Paris-Saclay, Université Côte d'Azur (UCA), University of Arizona, Laboratoire d'études spatiales et d'instrumentation en astrophysique (LESIA (UMR_8109)), Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institute of Astronomy [ETH Zürich], Department of Physics [ETH Zürich] (D-PHYS), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich)- Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), NOVA Optical Infrared Instrumentation Group, INAF - Osservatorio Astronomico di Padova (OAPD), Istituto Nazionale di Astrofisica (INAF), Max-Planck-Institut für Astronomie (MPIA), Max-Planck-Gesellschaft, Observatoire Astronomique de l'Université de Genève (ObsGE), Université de Genève = University of Geneva (UNIGE), Centre de Recherche Astrophysique de Lyon (CRAL), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), SRON Netherlands Institute for Space Research (SRON), Croissance et propriétés de systèmes hybrides en couches minces (INSP-E8), Institut des Nanosciences de Paris (INSP), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), European Southern Observatory (ESO), Space Sciences, Technologies and Astrophysics Research Institute (STAR), Université de Liège, Unité de recherche d'Économie et Sociologie Rurales (ESR), Institut National de la Recherche Agronomique (INRA), INAF - Osservatorio Astronomico di Roma (OAR), Universität Greifswald - University of Greifswald, European Southern Observatory [Santiago] (ESO), Immunopathologie et chimie thérapeutique (ICT), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institute for Astronomy [Edinburgh] (IfA), University of Edinburgh, INAF - Osservatorio Astronomico di Capodimonte (OAC), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de Cosmologie, Astrophysique Stellaire & Solaire, de Planétologie et de Mécanique des Fluides (CASSIOPEE), Institut d'Astrophysique de Paris (IAP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), INAF - Osservatorio Astrofisico di Arcetri (OAA), DOTA, ONERA, Université Paris Saclay [Palaiseau], Department of Astronomy, Stockholm University, Kapteyn Astronomical Institute [Groningen], University of Groningen [Groningen], Centre européen de recherche et d'enseignement des géosciences de l'environnement (CEREGE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Collège de France (CdF (institution))-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Sterrewacht Leiden, Astrophysique Relativiste Théories Expériences Métrologie Instrumentation Signaux (ARTEMIS), Laboratoire d'études spatiales et d'instrumentation en astrophysique (LESIA), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Aix Marseille Université (AMU)-Centre National d'Études Spatiales [Toulouse] (CNES), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Observatoire de la Côte d'Azur, COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Université Côte d'Azur (UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Observatoire de la Côte d'Azur, Université Côte d'Azur (UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Université Côte d'Azur (UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Universiteit Leiden
Subjects: Earth and Planetary Astrophysics (astro-ph.EP), [SDU.ASTR]Sciences of the Universe [physics]/Astrophysics [astro-ph], Astrophysics::Instrumentation and Methods for Astrophysics, FOS: Physical sciences, Astrophysics::Cosmology and Extragalactic Astrophysics, [PHYS.ASTR.CO]Physics [physics]/Astrophysics [astro-ph]/Cosmology and Extra-Galactic Astrophysics [astro-ph.CO], Astrophysics - Solar and Stellar Astrophysics, [SDU]Sciences of the Universe [physics], Astrophysics::Earth and Planetary Astrophysics, Astrophysics - Instrumentation and Methods for Astrophysics, [PHYS.ASTR]Physics [physics]/Astrophysics [astro-ph], Instrumentation and Methods for Astrophysics (astro-ph.IM), Solar and Stellar Astrophysics (astro-ph.SR), Astrophysics::Galaxy Astrophysics, Astrophysics - Earth and Planetary Astrophysics
Abstract: SPHERE (Beuzit et al,. 2019) has now been in operation at the VLT for more than 5 years, demonstrating a high level of performance. SPHERE has produced outstanding results using a variety of operating modes, primarily in the field of direct imaging of exoplanetary systems, focusing on exoplanets as point sources and circumstellar disks as extended objects. The achievements obtained thus far with SPHERE (~200 refereed publications) in different areas (exoplanets, disks, solar system, stellar physics...) have motivated a large consortium to propose an even more ambitious set of science cases, and its corresponding technical implementation in the form of an upgrade. The SPHERE+ project capitalizes on the expertise and lessons learned from SPHERE to push high contrast imaging performance to its limits on the VLT 8m-telescope. The scientific program of SPHERE+ described in this document will open a new and compelling scientific window for the upcoming decade in strong synergy with ground-based facilities (VLT/I, ELT, ALMA, and SKA) and space missions (Gaia, JWST, PLATO and WFIRST). While SPHERE has sampled the outer parts of planetary systems beyond a few tens of AU, SPHERE+ will dig into the inner regions around stars to reveal and characterize by mean of spectroscopy the giant planet population down to the snow line. Building on SPHERE's scientific heritage and resounding success, SPHERE+ will be a dedicated survey instrument which will strengthen the leadership of ESO and the European community in the very competitive field of direct imaging of exoplanetary systems. With enhanced capabilities, it will enable an even broader diversity of science cases including the study of the solar system, the birth and death of stars and the exploration of the inner regions of active galactic nuclei., White paper submitted to ESO on Feb. 20th, 2020
Published: 2020

38. Reconstitution in vitro des réponses immunitaires initiales dans la dermatite atopique

Author: Brulefert, Adrien, Immunopathologie et chimie thérapeutique (ICT), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg, and Vincent Flacher
Subjects: Thymic stromal lymphopoietin, T helper 2, Dermatite atopique, Modèle de peau reconstruite, [SDV.IMM]Life Sciences [q-bio]/Immunology, Cellule dendritique, Vitamine D3, Dendritic cell, Vitamin D3, Reconstructed skin model, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology, Atopic dermatitis
Abstract: Atopic dermatitis (AD) is a chronic cutaneous inflammation driven by T helper 2 cells (Th2) and characterized by a persistent itch. This response relies on Thymic Stromal Lymphopoietin (TSLP) production by keratinocytes and T cell orientation by TSLP-stimulated skin dendritic cells (DCs). Here, we propose new strategies to model AD pathogenesis in human systems. We validated vitamin D3 as an initiation stimulus for human TSLP-dependent Th2 (IL-13+) responses in healthy skin explants. In skin DCs and monocyte-derived DCs (MonoDCs), we showed that vitamin D3 provokes marked phenotypic alterations, characterized by CD14 expression. These cells specifically lead to TSLP-independent Th2 (IL-4+) orientation. In parallel, we have constructed a 3D skin model harboring DCs, sensory neurons and keratinocytes, in which we will evaluate whether vitamin D3 and other stimuli may induce Th2 responses, and how this might be regulated by neurons. This approach will help the rational design of AD-specific therapies.; La dermatite atopique (DA) est une maladie cutanée inflammatoire chronique, caractérisée par un infiltrat de lymphocytes T helper 2 (Th2) et une sensation de prurit. Cette réponse est sous influence du Thymic Stromal Lymphopoietin (TSLP), produit par les kératinocytes, qui affecte la capacité des cellules dendritiques (DCs) de la peau à orienter des lymphocytes T. Nous proposons ici de nouvelles stratégies pour modéliser la DA in vitro chez l’homme. Nous avons validé la vitamine D3 pour initier des réponses Th2 TSLP-dépendantes (IL-13+) sur des explants de peau saine. Dans les DCs de peau ou dérivées de monocytes (MonoDCs), nous avons démontré que la vitamine D3 provoque de profonds changements phénotypiques, caractérisés par l’expression du marqueur CD14. Ces cellules conduisent spécifiquement à une orientation Th2 (IL-4+) TSLP-indépendante. En parallèle, nous avons constitué un modèle 3D de peau contenant des DCs, des neurones et des kératinocytes, dans lequel nous évaluerons si la vitamine D3 et d’autres agents peuvent induire une réponse Th2, et si celle-ci peut être influencée par les neurones. Cette étude aidera à la conception de thérapies spécifiques de la DA.
Published: 2020

39. Is carboxylation an efficient method for graphene oxide functionalization?

Author: Jésus Raya, Shi Guo, Ding-Kun Ji, Alberto Bianco, Yuta Nishina, Cécilia Ménard-Moyon, Immunopathologie et chimie thérapeutique (ICT), Centre National de la Recherche Scientifique (CNRS)-Institut de biologie moléculaire et cellulaire (IBMC), and Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Research areas, Chloroacetic acid, Oxide, Epoxide, Bioengineering, 02 engineering and technology, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, 010402 general chemistry, 01 natural sciences, law.invention, chemistry.chemical_compound, law, [CHIM]Chemical Sciences, General Materials Science, epoxide ring opening, magic angle spinning NMR, ComputingMilieux_MISCELLANEOUS, Graphene, multifunctionalisation, General Engineering, General Chemistry, 021001 nanoscience & nanotechnology, 2D materials, Combinatorial chemistry, Atomic and Molecular Physics, and Optics, 0104 chemical sciences, chemistry, Carboxylation, Sodium hydroxide, Surface modification, Carbon nanomaterials, 0210 nano-technology
Abstract: Graphene oxide (GO) is one of the most popular materials applied in different research areas thanks to its unique properties. The application of GO requires well-designed protocols to introduce different functionalities on its surface, exploiting the oxygenated groups already present. Due to the complex and unstable chemical environment on the GO surface, it is recommended to perform the functionalization under mild conditions. The carboxylation of GO is a widely used method to introduce additional carboxylic acids, which could be further modified through amidation or esterification reactions. The strategy already reported in the literature requires harsh conditions (excess amount of sodium hydroxide). GO is readily reduced under basic conditions, but the reduction of GO during the carboxylation is barely studied. In this work, we performed the carboxylation using chloroacetic acid with different amounts of sodium hydroxide and characterized the functionalized GO with various techniques. The carboxylated GO was exploited to develop a double functionalization approach combining an epoxide ring opening reaction and an amidation. The results showed that strong basic conditions were necessary to derivatize GO. Nevertheless, these conditions resulted in a partial reduction of GO and some functionalities on GO were removed during the reaction, thus reducing the total efficiency of the functionalization in comparison to an epoxide ring opening reaction, indicating that carboxylation is not an efficient approach for the functionalization of GO.
Published: 2020
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40. Nose-to-Brain Translocation and Cerebral Biodegradation of Thin Graphene Oxide Nanosheets

Author: Alberto Bianco, Leon Newman, Artur Filipe Rodrigues, Isabella Anna Vacchi, Kostas Kostarelos, Dhifaf A. Jasim, Cécilia Ménard-Moyon, Cyrill Bussy, Immunopathologie et chimie thérapeutique (ICT), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), UK Research and Innovation, European Commission, Centre National de la Recherche Scientifique (France), Centre International de Recherche aux Frontières de la Chimie (France), Agence Nationale de la Recherche (France), Newman, Leon, Rodrigues, Artur Filipe, Jasim, Dhifaf, Bussy, Cyrill, Kostarelos, Kostas, Centre National de la Recherche Scientifique (CNRS)-Institut de biologie moléculaire et cellulaire (IBMC), and Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Lydia Becker Institute, nose-to-brain translocation, General Physics and Astronomy, Chromosomal translocation, 02 engineering and technology, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, biodegradation, Nanomaterials, law.invention, chemistry.chemical_compound, Biodistribution, law, General Materials Science, Thomas Ashton Institute, ResearchInstitutes_Networks_Beacons/MERI, Advanced Materials in Medicine, 0303 health sciences, inhalation, Chemistry, General Engineering, ResearchInstitutes_Networks_Beacons/03/02, ResearchInstitutes_Networks_Beacons/thomas_ashton_institute, Manchester Environmental Research Institute, 021001 nanoscience & nanotechnology, lcsh:QC1-999, General Energy, Biodegradation, symbols, graphene oxide, Advanced materials, 0210 nano-technology, Confocal, brain, Oxide, 03 medical and health sciences, symbols.namesake, National Graphene Institute, ResearchInstitutes_Networks_Beacons/lydia_becker_institute_of_immunology_and_inflammation, [CHIM]Chemical Sciences, 030304 developmental biology, Graphene, graphene, ResearchInstitutes_Networks_Beacons/02/12, General Chemistry, 2D materials, nose-brain translocation, ResearchInstitutes_Networks_Beacons/national_graphene_institute, Biophysics, Raman spectroscopy, lcsh:Physics
Abstract: Understanding the interactions of graphene oxide (GO)-based materials with biological systems is critical due to the potential applications of these materials. Here, we investigate the extent to which single- to few-layer GO sheets of different controlled lateral dimensions translocate from the nose to the brain following intranasal instillation. We explore tissue location and in vivo biodegradability of the translocated materials using various techniques. Mass spectrometry and confocal Raman analyses indicate that trace amounts of GO undergo nose-to-brain translocation in a size-dependent manner. The smallest GO-sheet size category (us-GO, 10-550 nm) gains the greatest access to the brain in terms of quantity and coverage. Confocal Raman mapping and immunofluorescence combinations show that in vivo, us-GO resides in association with microglia. Point-and-shoot Raman spectroscopy shows that trace quantities of us-GO are maintained over 1 month, but undergo biodegradation-related changes. This study adds to growing awareness regarding the fate of graphene-based materials in biological systems., This work was partially supported by the UKRI Engineering and Physical Sciences Research Council (UKRI EPSRC) NowNano Centre for Doctoral Training programs (EP/K016946/1 and EP/M010619/1), and the European Union (EU) 7th and 8th Framework Programmes for Research and Technological Development, Graphene Flagship project (FP7-ICT-2013-FET-F-604391 and H2020-FET-696656–Graphene Core 1). We gratefully acknowledge the Centre National de la Recherche Scientifique (CNRS), the International Center for Frontier Research in Chemistry (icFRC), and financial support from the Agence Nationale de la Recherche (ANR) through the LabEx project Chemistry of Complex Systems (ANR-10-LABX-0026_CSC).
Published: 2020
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41. Comparative Effects of Graphene and Molybdenum Disulfide on Human Macrophage Toxicity

Author: Paolo Samorì, Alberto Bianco, Ding-Kun Ji, Hazel Lin, Matteo Andrea Lucherelli, Giacomo Reina, Stefano Ippolito, Immunopathologie et chimie thérapeutique (ICT), Institut de biologie moléculaire et cellulaire (IBMC), and Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 02 engineering and technology, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Filaggrin Proteins, 010402 general chemistry, 01 natural sciences, Proinflammatory cytokine, Biomaterials, Immune system, Gene expression, Macrophage, Humans, [CHIM]Chemical Sciences, General Materials Science, Secretion, Disulfides, Cytotoxicity, Molybdenum, Chemistry, Macrophages, General Chemistry, 021001 nanoscience & nanotechnology, M2 Macrophage, 0104 chemical sciences, Cell biology, Blot, Graphite, 0210 nano-technology, Biotechnology
Abstract: International audience; Graphene and other two-dimensional (2D) materials, such as molybdenum disulfide, have been increasingly used in electronics, composites and biomedicine. In particular, MoS2 and graphene hybrids have attracted a great interest for applications in the biomedical research, therefore stimulating a pertinent investigation on their safety in immune cells like macrophages, which commonly engulf these materials. In our study, M1 and M2 macrophage viability and activation were mainly found to be unaffected by few-layer graphene (FLG) and MoS2 at doses up to 50 µg/mL. The uptake of both materials was confirmed by transmission electron microscopy, inductively coupled plasma mass spectrometry and inductively coupled plasma atomic emission spectroscopy. Notably, both 2D materials increased the secretion of inflammatory cytokines in M1 macrophages. At the highest dose, FLG decreased CD206 expression while MoS2 decreased CD80 expression. CathB and CathL gene expression were dose-dependently increased by both materials. Despite a minimal impact on the autophagic pathway, FLG was found to increase the expression of Atg5 and autophagic flux, as observed by western blotting of LC3-II, in M1 macrophages. Overall, FLG and MoS2 are little toxic in human macrophages even though they were found to trigger cell stress and inflammatory responses. 2
Published: 2020
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42. Degradation-by-design: how chemical functionalization enhances the biodegradability and safety of 2D materials

Author: Cristina Martín, Rajendra Kurapati, Alberto Bianco, Baojin Ma, Immunopathologie et chimie thérapeutique (ICT), Centre National de la Recherche Scientifique (CNRS)-Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie moléculaire et cellulaire (IBMC), and Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Materials science, Context (language use), Nanotechnology, Biocompatible Materials, 02 engineering and technology, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, 010402 general chemistry, 01 natural sciences, Drug Delivery Systems, [CHIM]Chemical Sciences, ComputingMilieux_MISCELLANEOUS, Bioelectronics, therapy, graphene, toxicity, imaging, General Chemistry, Biodegradation, 021001 nanoscience & nanotechnology, 0104 chemical sciences, Biodegradation, Environmental, Chemical functionalization, Drug delivery, Degradation (geology), Carbon nanomaterials, Graphite, 0210 nano-technology, MXenes, Potential toxicity
Abstract: A large number of graphene and other 2D materials are currently used for the development of new technologies, increasingly entering different industrial sectors. Interrogating the impact of such 2D materials on health and environment is crucial for both modulating their potential toxicity in living organisms and eliminating them from the environment. In this context, understanding if 2D materials are bio-persistent is mandatory. In this review we describe the importance of biodegradability and decomposition of 2D materials. We initially cover the biodegradation of graphene family materials, followed by other emerging classes of 2D materials including transition metal dichalcogenides and oxides, Xenes, Mxenes and other non-metallic 2D materials. We explain the role of defects and functional groups, introduced onto the surface of the materials during their preparation, and the consequences of chemical functionalization on biodegradability. In strong relation to the chemistry on 2D materials, we describe the concept of "degradation-by-design" that we contributed to develop, and which concerns the covalent modification with appropriate molecules to enhance the biodegradability of 2D materials. Finally, we cover the importance of designing new biodegradable 2D conjugates and devices for biomedical applications as drug delivery carriers, in bioelectronics, and tissue engineering. We would like to highlight that the biodegradation of 2D materials mainly depends on the type of material, the chemical functionalization, the aqueous dispersibility and the redox potentials of the different oxidative environments. Biodegradation is one of the necessary conditions for the safe application of 2D materials. Therefore, we hope that this review will help to better understand their biodegradation processes, and will stimulate the chemists to explore new chemical strategies to design safer products, composites and devices containing 2D materials.
Published: 2020
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43. Hard Nanomaterials in Time of Viral Pandemics

Author: Alberto Bianco, Lucas Jacquemin, Andrés Felipe Andrade, Shiyuan Peng, Giacomo Reina, Immunopathologie et chimie thérapeutique (ICT), Institut de biologie moléculaire et cellulaire (IBMC), and Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Human immunodeficiency virus (HIV), Metal Nanoparticles, General Physics and Astronomy, surface chemistry, Review, 02 engineering and technology, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Adaptive Immunity, medicine.disease_cause, 01 natural sciences, Drug Delivery Systems, vaccine, Pandemic, Nanotechnology, General Materials Science, ComputingMilieux_MISCELLANEOUS, virucidal, General Engineering, 021001 nanoscience & nanotechnology, antiviral, 3. Good health, Fullerenes, Coronavirus Infections, 0210 nano-technology, biomaterials, 2019-20 coronavirus outbreak, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Pneumonia, Viral, Context (language use), Biology, 010402 general chemistry, Antiviral Agents, Models, Biological, Virus, Betacoronavirus, medicine, Humans, [CHIM]Chemical Sciences, Pandemics, Host Microbial Interactions, SARS-CoV-2, COVID-19, Virus Internalization, Virology, Immunity, Innate, Nanostructures, 0104 chemical sciences, immune system, nanoparticles, Reactive Oxygen Species, phototherapy, Material chemistry
Abstract: The SARS-Cov-2 pandemic has spread worldwide during 2020, setting up an uncertain start of this decade. The measures to contain infection taken by many governments have been extremely severe by imposing home lockdown and industrial production shutdown, making this the biggest crisis since the second world war. Additionally, the continuous colonization of wild natural lands may touch unknown virus reservoirs, causing the spread of epidemics. Apart from SARS-Cov-2, the recent history has seen the spread of several viral pandemics such as H2N2 and H3N3 flu, HIV, and SARS, while MERS and Ebola viruses are considered still in a prepandemic phase. Hard nanomaterials (HNMs) have been recently used as antimicrobial agents, potentially being next-generation drugs to fight viral infections. HNMs can block infection at early (disinfection, entrance inhibition) and middle (inside the host cells) stages and are also able to mitigate the immune response. This review is focused on the application of HNMs as antiviral agents. In particular, mechanisms of actions, biological outputs, and limitations for each HNM will be systematically presented and analyzed from a material chemistry point-of-view. The antiviral activity will be discussed in the context of the different pandemic viruses. We acknowledge that HNM antiviral research is still at its early stage, however, we believe that this field will rapidly blossom in the next period.
Published: 2020
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44. Partial Reversibility of the Cytotoxic Effect Induced by Graphene-Based Materials in Skin Keratinocytes

Author: Hazel Lin, Cristina Ponti, Arianna Gazzi, Amaya Ortega, Amaia Zurutuza, Alberto Bianco, Ester Vázquez, Aurelia Tubaro, Silvio Sosa, Marco Pelin, Maurizio Prato, Pelin, Marco, Lin, Hazel, Gazzi, Arianna, Sosa, Silvio, Ponti, Cristina, Ortega, Amaya, Zurutuza, Amaia, Vázquez, Ester, Prato, Maurizio, Tubaro, Aurelia, Bianco, Alberto, Immunopathologie et chimie thérapeutique (ICT), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut de biologie moléculaire et cellulaire (IBMC), and Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: autophagy, Biocompatibility, General Chemical Engineering, media_common.quotation_subject, 2D material, 02 engineering and technology, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, 010402 general chemistry, medicine.disease_cause, 01 natural sciences, Article, lcsh:Chemistry, biocompatibility, medicine, Cytotoxic T cell, [CHIM]Chemical Sciences, General Materials Science, Viability assay, Internalization, Cytotoxicity, media_common, carbon nanomaterials, Chemistry, carbon nanomaterial, Autophagy, 021001 nanoscience & nanotechnology, 2D materials, dermal toxicity, 0104 chemical sciences, nervous system diseases, HaCaT, lcsh:QD1-999, Biophysics, 0210 nano-technology, Oxidative stress
Abstract: International audience; In the frame of graphene-based material (GBM) hazard characterization, particular attention should be given to the cutaneous effects. Hence, this study investigates if HaCaT skin keratinocytes exposed to high concentrations of few-layer graphene (FLG) or partially dehydrated graphene oxide (d-GO) for a short time can recover from the cytotoxic insult, measured by means of cell viability, mitochondrial damage and oxidative stress, after GBM removal from the cell medium. When compared to 24 or 72 h continuous exposure, recovery experiments suggest that the cytotoxicity induced by 24 h exposure to GBM is only partially recovered after 48 h culture in GBM-free medium. This partial recovery, higher for FLG as compared to GO, is not mediated by autophagy and could be the consequence of GBM internalization into cells. The ability of GBMs to be internalized inside keratinocytes together with the partial reversibility of the cellular damage is important in assessing the risk associated with skin exposure to GBM-containing devices.
Published: 2020
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45. Controlled Functionalization of Carbon Nanodots for Targeted Intracellular Production of Reactive Oxygen Species

Author: Matilde Eredia, Paolo Samorì, Ding-Kun Ji, Alberto Bianco, Shi Guo, Giacomo Reina, Cécilia Ménard-Moyon, Immunopathologie et chimie thérapeutique (ICT), Centre National de la Recherche Scientifique (CNRS)-Institut de biologie moléculaire et cellulaire (IBMC), and Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Programmed cell death, Light, medicine.medical_treatment, Photodynamic therapy, 02 engineering and technology, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, 010402 general chemistry, 01 natural sciences, Folic Acid, Quantum Dots, medicine, Humans, [CHIM]Chemical Sciences, General Materials Science, ComputingMilieux_MISCELLANEOUS, Fluorescent Dyes, chemistry.chemical_classification, Reactive oxygen species, Photosensitizing Agents, Optical Imaging, 021001 nanoscience & nanotechnology, Ligand (biochemistry), Carbon, 0104 chemical sciences, 3. Good health, chemistry, Cancer cell, Biophysics, Surface modification, Nanodot, Reactive Oxygen Species, 0210 nano-technology, Intracellular, HeLa Cells
Abstract: Controlled intracellular release of exogenous reactive oxygen species (ROS) is an innovative and efficient strategy for cancer treatment. Well-designed materials, which can produce ROS in targeted cells, minimizing side effects, still need to be explored as new generation nanomedicines. Here, red-emissive carbon nanodots (CNDs) with intrinsic theranostic properties are devised, and further modified with folic acid (FA) ligand through a controlled covalent functionalization for targeted cell imaging and intracellular production of ROS. We demonstrated that covalent functionalization is an effective strategy to prevent the aggregation of the dots, leading to superior colloidal stability, enhanced luminescence and ROS generation. Indeed, the functional nanodots possess a deep-red emission and good dispersibility under physiological conditions. Importantly, they show excellent targeting properties and generation of high levels of ROS under 660 nm laser irradiation, leading to efficient cell death. These unique properties enable FA-modified carbon nanodots to act as a multifunctional nanoplatform for simultaneous targeted imaging and efficient photodynamic therapy to induce cancer cell death.
Published: 2020
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46. Différenciation et culture tridimensionnelle de neurones sensoriels humains et de cellules de Schwann dans un modèle de peau reconstruit par génie tissulaire

Author: Quentin Muller, Marie-Josée Beaudet, Valérie Chaumet, Thiéry de Serres-Bérard, Sabrina Bellenfant, Vincent FLACHER, François Berthod, Université Laval [Québec] (ULaval), Immunologie et chimie thérapeutiques (ICT), Cancéropôle du Grand Est-Centre National de la Recherche Scientifique (CNRS), Immunopathologie et chimie thérapeutique (ICT), Centre National de la Recherche Scientifique (CNRS)-Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie moléculaire et cellulaire (IBMC), and Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SDV.BIO]Life Sciences [q-bio]/Biotechnology, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2020

47. Degradation of Structurally Defined Graphene Nanoribbons by Myeloperoxidase and the Photo-Fenton Reaction

Author: Lucia Gemma Delogu, Pengfei Zhang, Alberto Bianco, Yiyong Mai, Isabella Anna Vacchi, Qian Li, Cristina Martín, Xiangfeng Luan, Immunopathologie et chimie thérapeutique (ICT), Centre National de la Recherche Scientifique (CNRS)-Institut de biologie moléculaire et cellulaire (IBMC), and Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Materials science, 02 engineering and technology, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, biodegradability, carbon materials, hydroxyl radicals, peroxidases, photo-Fenton reaction, 010402 general chemistry, Photochemistry, 01 natural sciences, Catalysis, law.invention, chemistry.chemical_compound, law, [CHIM]Chemical Sciences, Imidazole, Functionalization, Potassium hydroxide, Aqueous solution, biology, 010405 organic chemistry, Graphene, General Medicine, General Chemistry, Biodegradation, 021001 nanoscience & nanotechnology, 0104 chemical sciences, chemistry, Myeloperoxidase, biology.protein, Surface modification, 0210 nano-technology, Graphene nanoribbons
Abstract: International audience; As an emerging member of the graphene family, structurally defined graphene nanoribbons (GNRs) have shown promising applications in various fields. The evaluation of the degradability of GNRs is particularly important for assessing the persistence level and risk of these materials in living organisms and the environment. However, there is a void in the study of the degradation of GNRs. Here, we report the degradation behavior of GNRs in the presence of human myeloperoxidase (hMPO) or treated with photo-Fenton (PF) reaction. With the assistance of potassium hydroxide or imidazole, which facilitates the dispersion of GNRs in the aqueous solution, GNRs underwent only partial degradation after 25-hour incubation with hMPO, while, the PF reaction degraded GNRs almost completely after 120 hours. These results indicate that structurally precise GNRs can be efficiently degraded under suitable conditions, providing more opportunities for future applications in different fields.
Published: 2020
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48. Neutron-irradiated antibody-functionalised carbon nanocapsules for targeted cancer radiotherapy

Author: Rebecca Klippstein, Aritz Perez Ruiz de Garibay, Gerard Tobias, Ioanna Kyriakou, Markus Martincic, Jean-Claude Saccavini, Cinzia Spinato, Martin Šefl, Pedro M. Costa, Alberto Bianco, Cécilia Ménard-Moyon, Robert Feldman, Yves Michel, Dimitris Emfietzoglou, Elzbieta Pach, Julie Tzu-Wen Wang, Khuloud T. Al-Jamal, Belén Ballesteros, Immunopathologie et chimie thérapeutique (ICT), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), European Commission, Wellcome Trust, Worldwide Cancer Research, Centre National de la Recherche Scientifique (France), Agence Nationale de la Recherche (France), Centre International de Recherche aux Frontières de la Chimie (France), Ministerio de Economía y Competitividad (España), Centre National de la Recherche Scientifique (CNRS)-Institut de biologie moléculaire et cellulaire (IBMC), and Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Biodistribution, Intravenous injections, medicine.medical_treatment, Spleen, 02 engineering and technology, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, 010402 general chemistry, 01 natural sciences, Nanocapsules, Ionizing radiation, Surface functionalisation, Epidermal growth factor receptors, medicine, General Materials Science, Epidermal growth factor receptor, Nanotubes, Cancer radiotherapies, biology, Chemistry, Radiochemistry, General Chemistry, Gel electrophoresis, 021001 nanoscience & nanotechnology, Chemical functionalisation, Therapeutic efficacy, Silica nanoparticles, Antibody conjugation, 3. Good health, 0104 chemical sciences, Radiation therapy, medicine.anatomical_structure, Cancer cell, biology.protein, Chimie/Chimie thérapeutique, Therapy, Antibody, 0210 nano-technology, Delivery
Abstract: Radiotherapy is a cancer treatment utilising high doses of ionizing radiation to destroy cancer cells. Our team has pioneered neutron activation of 152Sm, filled and sealed into single-walled (SWCNTs) and multi-walled carbon nanotubes (MWCNTs), to create stable and high-dose radioactive carbon nanocapsules for cancer radiotherapy. In this work, MWCNTs filled with enriched 152SmCl3 (Sm@MWCNTs) were sealed and irradiated, followed by surface functionalisation with an epidermal growth factor receptor (EGFR)-targeting antibody. Characterisation of functionalised Sm@MWCNTs was carried out using thermogravimetric analysis, gel electrophoresis and transmission electron microscopy. The organ biodistribution of the radioactive functionalised 153Sm@MWCNTs and therapeutic efficacy were studied in an experimental melanoma lung metastatic tumour model in mice after intravenous injection. Quantitative biodistribution analyses showed high accumulation of 153Sm@MWCNT-Ab in lung. Significant tumour growth reduction was induced by both treatments of 153Sm@MWCNTs functionalised with or without the antibody after a single intravenous injection. Although EGFR targeting showed no improvement in therapeutic efficacy, reduced spleen toxicity and normal haematological profiles were obtained for both functionalised derivatives. The current study demonstrated the possibility of performing chemical functionalisation and antibody conjugation on radioactive nanocapsules post-irradiation for the preparation of targeted radiopharmaceuticals., This work received funding from the European Union’s Seventh Framework Programme (FP7-ITN Marie-Curie Actions, RADDEL, 290023). PM Costa would like to acknowledge the funding from the Wellcome Trust (WT103913). KT A-J would like to acknowledge the funding from Worldwide Cancer Research, UK (12–1054). This work was partly supported by the Centre National de la Recherche Scientifique (CNRS), Agence Nationale de la Recherche (ANR) through the LabEx project Chemistry of Complex Systems (ANR-10-LABX-0026_CSC), and the International Center for Frontier Research in Chemistry (icFRC). ICMAB and ICN2 acknowledge financial support from the Spanish Ministry of Economy and Competitiveness, through the “Severo Ochoa” Programme for Centres of Excellence in R&D (SEV-2015-0496 and SEV-2017-0706). We thank Thomas Swan Co. Ltd. for supplying CNT Elicarb® samples. We wish to acknowledge Cathy Royer and Valérie Demais for TEM analyses at the Plateforme Imagerie in Vitro at the Center of Neurochemistry (Strasbourg, France).
Published: 2020
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49. Worldwide trends in all-cause mortality of auto-immune systemic diseases between 2001 and 2014

Author: Alain Meyer, Christophe Richez, Thierry Martin, Emmanuel Chatelus, Marc Scherlinger, Laurent Arnaud, Christelle Sordet, Hervé Devillers, Renaud Felten, Flora Sagez, Vincent Poindron, Rose-Marie Javier, Thierry Schaeverbeke, Jean Sibilia, Aurélien Guffroy, Patrick Blanco, Marie-Elise Truchetet, Anne-Sophie Korganow, Philippe Mertz, Mitochondrie, stress oxydant et protection musculaire (MSP), Université de Strasbourg (UNISTRA), Immuno-Rhumatologie Moléculaire, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA), Immunopathologie et chimie thérapeutique (ICT), Institut de biologie moléculaire et cellulaire (IBMC), and Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, medicine.medical_specialty, Internationality, Immunology, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Disease, Autoimmune Diseases, 03 medical and health sciences, symbols.namesake, 0302 clinical medicine, Mixed connective tissue disease, Internal medicine, Cause of Death, Epidemiology, medicine, Immunology and Allergy, Humans, Lupus Erythematosus, Systemic, Poisson regression, Mixed Connective Tissue Disease, 030203 arthritis & rheumatology, Scleroderma, Systemic, Myositis, business.industry, Mortality rate, medicine.disease, Confidence interval, 3. Good health, 030104 developmental biology, Sjogren's Syndrome, symbols, [SDV.IMM]Life Sciences [q-bio]/Immunology, business, Vasculitis, All cause mortality
Abstract: To describe changes in the 2001-2014 mortality of 6 autoimmune systemic diseases (AISDs), namely Systemic Lupus Erythematosus (SLE), Systemic Sclerosis (SSc), Idiopathic Inflammatory Myopathies (IIM), Sjögren's Syndrome (SS), Mixed Connective Tissue Disease (MCTD) and ANCA-associated vasculitis (AAV) at the country-, continent-, and world-levels.Mortality data were retrieved from the World Health Organization (WHO) mortality database for each disease, based on ICD-10 codes. We computed age-standardized mortality rate (ASMR) as the estimated number of deaths per million inhabitants and its 95% confidence interval (95%CI). The association between gender, geographical areas and disease-specific mortality was analyzed using multivariate Poisson regression. The 2001-2014 temporal trends were analyzed using Jointpoint software.In 2014, the worldwide ASMR for SLE was 2.68 (95%CI: 2.62-2.75) deaths/millions inhabitants, 1.46 (1.42-1.51) for SSc, 0.47 (0.44-0.49) for IIM, 0.17 (0.15-0.18) for SS, 0.11 (0.10-0.13) for MCTD and 0.53 (0.50-0.56) for AAV, with ASMRs generally lower in Europe than in North America, Latin America and Asia. Between 2001 and 2014, the worldwide ASMR decreased significantly for SSc (-0.71%/year), IIM (-1.65%/year) and AAV (-1.01%/year; p .001 for all) and increased for SS (+1.53%/year, p = .01). The worldwide ASMR of SLE decreased significantly between 2001 and 2003 (-6.37%, p .05) before increasing slightly between 2004 and 2014 (+0.58%, p .01).We observed a strong heterogeneity of standardized mortality rates across all countries analyzed for 6 autoimmune diseases. Those results further highlight the impact of world-wide inequities and major gaps in access to care and strategies for diagnosis and management of rare diseases, a crucial finding for world-wide physicians, patient associations and policy makers.
Published: 2020
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50. Immune Defect in Adults With Down Syndrome: Insights Into a Complex Issue

Author: Yannick Dieudonné, Beatrice Uring-Lambert, Mohamed Maxime Jeljeli, Vincent Gies, Yves Alembik, Anne-Sophie Korganow, Aurélien Guffroy, Immunopathologie et chimie thérapeutique (ICT), Centre National de la Recherche Scientifique (CNRS)-Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Immuno-Rhumatologie Moléculaire, and Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Adult, Male, 0301 basic medicine, lcsh:Immunologic diseases. Allergy, Down syndrome, down syndrome, adulthood, Adolescent, T-Lymphocytes, Lymphocyte, Immunology, Infections, medicine.disease_cause, primary immunodeficiency, Autoimmunity, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Immune system, Antigen, medicine, Humans, Immunology and Allergy, Sciences du Vivant [q-bio]/Immunologie, Immunodeficiency, Original Research, B-Lymphocytes, business.industry, autoimmunity, Immunologic Deficiency Syndromes, Middle Aged, medicine.disease, infectious risk, 3. Good health, Phenotype, 030104 developmental biology, medicine.anatomical_structure, Primary immunodeficiency, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, business, lcsh:RC581-607, Immunologic Memory, Memory T cell, 030215 immunology
Abstract: Children with Down syndrome (DS) suffer from recurrent respiratory infections, which represent the leading cause of mortality during childhood. This susceptibility to infections is usually considered multifactorial and related to both impaired immune function and non-immunological factors. Infections are also one of the top causes of death in DS at adulthood. DS is considered an immunodeficiency with syndromic features by some researchers because of this high rate of infection and the immunological characteristics observed in children with DS. Little is known about the immune status of adult patients. Herein, we report the clinical and immune phenotype of 44 adults with DS, correlated with their infectious history. We observed that these adults had an aberrant lymphocyte phenotype with decreased naïve/memory T cell ratios and reduced numbers of switched memory B cells. The lower incidence of infectious events at adulthood distinguish DS from other inborn errors of immunity. Primary immunodeficiency-related features in DS could explain the increased risk of developing autoimmunity, malignancies, and infections. During adulthood, this immune dysfunction may be compensated for in mid-life, and infection-related mortality observed in older patients might be favored by multiple factors such as neurological impairment or nosocomial antigen exposure. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT01663675 (August 13, 2012).
Published: 2020
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