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55. Crosstalk between neutrophils, B-1a cells and plasmacytoid dendritic cells initiates autoimmune diabetes

Author

Diana, Julien, Simoni, Yannick, Furio, Laetitia, Beaudoin, Lucie, Agerberth, Birgitta, Barrat, Franck, and Lehuen, Agnes

Subjects
Autoimmunity -- Research, Type 1 diabetes -- Development and progression, Neutrophils -- Health aspects, Dendritic cells -- Health aspects, Biological sciences, Health
Abstract

Type 1 diabetes develops over many years and is characterized ultimately by the destruction of insulin-producing pancreatic beta cells by autoreactive T cells. Nonetheless, the role of innate cells in the initiation of this disease remains poorly understood. Here, we show that in young female nonobese diabetic mice, physiological beta cell death induces the recruitment and activation of B-1a cells, neutrophils and plasmacytoid dendritic cells (pDCs) to the pancreas. Activated B-1a cells secrete IgGs specific for double-stranded DNA. IgGs activate neutrophils to release DNA-binding cathelicidin-related antimicrobial peptide (CRAMP), which binds self DNA. Then, self DNA, DNA-specific IgG and CRAMP peptide activate pDCs through the Toll-like receptor 9-myeloid differentiation factor 88 pathway, leading to interferon-α production in pancreatic islets. We further demonstrate through the use of depleting treatments that B-1a cells, neutrophils and IFN-α-producing pDCs are required for the initiation of the diabetogenic T cell response and type 1 diabetes development. These findings reveal that an innate immune cell crosstalk takes place in the pancreas of young NOD mice and leads to the initiation of T1D., T cells infiltrate the pancreas and target insulin-producing beta cells during type 1 diabetes (T1D) development (1). However, T cells represent only one piece of the puzzle of the multiple [...]

Published
2013
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57. MAIT cells, guardians of skin and mucosa?

Author

Amine Toubal, Isabelle Nel, Agnès Lehuen, Léo Bertrand, Université de Paris, Institut Cochin, INSERM U1016, CNRS UMR 8104, Université de Paris, Paris, France, Laboratoire d’Excellence Inflamex, Paris, France, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), and ROULAND, Matthieu

Subjects
0301 basic medicine, Vitamin b, [SDV]Life Sciences [q-bio], Immunology, Gene Expression, Review Article, Biology, Mucosal-Associated Invariant T Cells, 03 medical and health sciences, 0302 clinical medicine, Immune system, Immunology and Allergy, Animals, Homeostasis, Humans, Respiratory system, ComputingMilieux_MISCELLANEOUS, Skin, Mucous Membrane, Host Microbial Interactions, MAIT Cells, 3. Good health, [SDV] Life Sciences [q-bio], 030104 developmental biology, Phenotype, Organ Specificity, Cytokines, Disease Susceptibility, Biomarkers, 030215 immunology
Abstract

Mucosal Associated Invariant T (MAIT) cells are evolutionary conserved innate-like T cells able to recognize bacterial and fungal ligands derived from vitamin B biosynthesis. These cells are particularly present in liver and blood but also populate mucosal sites including skin, oral, intestinal, respiratory, and urogenital tracts that are in contact with the environment and microbiota of their host. Growing evidence suggests important involvement of MAIT cells in safeguarding the mucosa against external microbial threats. Simultaneously, mucosal MAIT cells have been implicated in immune and inflammatory pathologies affecting these organs. Here, we review the specificities of mucosal MAIT cells, their functions in the protection and maintenance of mucosal barriers, and their interactions with other mucosal cells.

Published
2021
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58. Gut mucosa alterations and loss of segmented filamentous bacteria in type 1 diabetes are associated with inflammation rather than hyperglycaemia

Author

Philippe J. Sansonetti, Matthieu Rouland, Maria Rescigno, Lucie Cagninacci, Nathalie Vergnolle, Sandra Guilmeau, Juliette Mouriès, Latif Rachdi, Lucie Beaudoin, Azadeh Saffarian, Agnès Lehuen, Dalale Gueddouri, Anne-Françoise Burnol, Ute Christine Rogner, Asmaa Tazi, Ophélie Rouxel, Léo Bertrand, Thierry Pedron, Centre National de la Recherche Scientifique (CNRS), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Pathogénie microbienne moléculaire, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Humanitas University [Milan] (Hunimed), Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), LabEx Inflamex, This work was supported by Agence Nationale de la Recherche (ANR-11-IDEX-0005-02 Laboratory of Excellence INFLAMEX and ANR-17-CE14-0002-01 Diab1MAIT), Fondation pour la Recherche Médicale (DEQ20140329520 and EQU201903007779), the INSERM crosscutting program on microbiota and the European Foundation for the Study of Diabetes–Juvenile Diabetes Research Foundation–MR, OR and LBer were supported by the French Ministry of Research., ANR-11-IDEX-0005,USPC,Université Sorbonne Paris Cité(2011), ANR-17-CE14-0002,Diab1MAIT,Rôle des cellules MAIT dans le diabète de type 1 chez l'homme et la souris(2017), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Fondation pour la Recherche Medicale (DEQ20140329520 and EQU201903007779), European Foundation for the Study of Diabetes-Juvenile Diabetes Research Foundation-MR, OR and LBer are supported by the French Ministry of Research, and the INSERM crosscutting program on microbiota is supported by the French Ministry of Research

Subjects
0301 basic medicine, endocrine system diseases, medicine.medical_treatment, Segmented filamentous bacteria, intestinal microbiology, Inflammation, Gut flora, digestive system, Mice, 03 medical and health sciences, 0302 clinical medicine, Immune system, Diabetes Mellitus, medicine, Animals, Intestinal Mucosa, Autoimmune disease, Bacteria, biology, Insulin, digestive, oral, and skin physiology, Gastroenterology, Interleukin, Epithelial Cells, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, biology.organism_classification, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Gastrointestinal Microbiome, 3. Good health, Disease Models, Animal, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Diabetes Mellitus, Type 1, 030104 developmental biology, Hyperglycemia, 030220 oncology & carcinogenesis, Immunology, mucosal immunity, Cytokines, Dysbiosis, [SDV.IMM]Life Sciences [q-bio]/Immunology, medicine.symptom, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

ObjectiveType 1 diabetes (T1D) is an autoimmune disease caused by the destruction of pancreatic β-cells producing insulin. Both T1D patients and animal models exhibit gut microbiota and mucosa alterations, although the exact cause for these remains poorly understood. We investigated the production of key cytokines controlling gut integrity, the abundance of segmented filamentous bacteria (SFB) involved in the production of these cytokines, and the respective role of autoimmune inflammation and hyperglycaemia.DesignWe used several mouse models of autoimmune T1D as well as mice rendered hyperglycaemic without inflammation to study gut mucosa and microbiota dysbiosis. We analysed cytokine expression in immune cells, epithelial cell function, SFB abundance and microbiota composition by 16S sequencing. We assessed the role of anti-tumour necrosis factor α on gut mucosa inflammation and T1D onset.ResultsWe show in models of autoimmune T1D a conserved loss of interleukin (IL)-17A, IL-22 and IL-23A in gut mucosa. Intestinal epithelial cell function was altered and gut integrity was impaired. These defects were associated with dysbiosis including progressive loss of SFB. Transfer of diabetogenic T-cells recapitulated these gut alterations, whereas induction of hyperglycaemia with no inflammation failed to do so. Moreover, anti-inflammatory treatment restored gut mucosa and immune cell function and dampened diabetes incidence.ConclusionOur results demonstrate that gut mucosa alterations and dysbiosis in T1D are primarily linked to inflammation rather than hyperglycaemia. Anti-inflammatory treatment preserves gut homeostasis and protective commensal flora reducing T1D incidence.

Published
2021
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59. Invariant NKT cells regulate the CD8 T cell response during Theiler's virus infection.

Author

Lennart T Mars, Magali Mas, Lucie Beaudoin, Jan Bauer, Maria Leite-de-Moraes, Agnès Lehuen, Jean-Francois Bureau, and Roland S Liblau

Subjects
Medicine, Science
Abstract

Invariant NKT cells are innate lymphocytes with a broad tissue distribution. Here we demonstrate that iNKT cells reside in the central nervous system (CNS) in the absence of inflammation. Their presence in the CNS dramatically augments following inoculation of C57Bl/6 mice with the neurotropic Theiler's murine encephalomyelitis virus (TMEV). At the peak of inflammation the cellular infiltrate comprises 45,000 iNKT cells for 1250 CD8 T cells specific for the immunodominant TMEV epitope. To study the interaction between these two T cell subsets, we infected both iNKT cell deficient Jα18(-/-) mice and iNKT cell enriched Vα14 transgenic mice with TMEV. The CD8 T cell response readily cleared TMEV infection in the iNKT cell deficient mice. However, in the iNKT cell enriched mice TMEV infection persisted and was associated with significant mortality. This was caused by the inhibition of the CD8 T cell response in the cervical lymph nodes and spleen after T cell priming. Taken together we demonstrate that iNKT cells reside in the CNS in the absence of inflammation and that their enrichment is associated with the inhibition of the anti-viral CD8 T cell response and an augmented mortality during acute encephalomyelitis.

Published
2014
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61. Cytotoxic and regulatory roles of mucosal-associated invariant T cells in type 1 diabetes

Author

Olivier Lantz, Isabelle Nel, Jennifer Da Silva, Michel Polak, Lucie Beaudoin, Marc Diedisheim, Raphael Scharfmann, Badr Kiaf, Jacques Beltrand, Manuela Battaglia, Ophélie Rouxel, Marion Salou, Alexandra J. Corbett, Agnès Lehuen, Céline Tard, Masaya Oshima, James McCluskey, Lucie Cagninacci, Jamie Rossjohn, 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), Laboratoire d'excellence Inflamex, Sorbonne Paris Cité, Immunité et cancer (U932), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Monash University [Clayton], Cardiff University, University of Melbourne, San Raffaele Scientific Institute, Vita-Salute San Raffaele University and Center for Translational Genomics and Bioinformatics, San Raffaele Hospital, Service d'endocrinologie, gynécologie et diabétologie pédiatriques [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), and Lehuen, Agnès

Subjects
0301 basic medicine, [SDV.IMM] Life Sciences [q-bio]/Immunology, Immunology, Mucosal associated invariant T cell, Major histocompatibility complex, medicine.disease_cause, Granzymes, Mucosal-Associated Invariant T Cells, Autoimmunity, Minor Histocompatibility Antigens, Mice, 03 medical and health sciences, Immune system, Mice, Inbred NOD, Insulin-Secreting Cells, medicine, Animals, Humans, Immunology and Allergy, Cytotoxic T cell, Intestinal Mucosa, Pancreas, Cells, Cultured, NOD mice, biology, Histocompatibility Antigens Class I, Gastrointestinal Microbiome, 3. Good health, Mice, Inbred C57BL, Granzyme B, Diabetes Mellitus, Type 1, 030104 developmental biology, Granzyme, biology.protein, [SDV.IMM]Life Sciences [q-bio]/Immunology
Abstract

International audience; Type 1 diabetes (T1D) is an autoimmune disease characterized by the selective destruction of pancreatic islet β-cells that produce insulin, in the context of an underlying multigenetic inheritance 1. When most of the β-cells are destroyed or non-functional, the ensuing lack of insulin results in hyperglycemia and requires lifelong insulin-replacement therapy 1. The physiopathology of T1D involves inappropriate activation of both the innate immune system and adaptive immune system, which induces loss of self-tolerance and islet destruction 2-5. T1D is characterized by the presence of anti-islet autoantibodies and auto-reactive T cells. Innate immune cells are involved at various stages of the disease and are particularly important for the initiation of the local immune response in the pancreas and the pancreatic lymph nodes (PLNs) 2,4. Published data have highlighted the role of the intestinal microbiota in T1D by transfer experiments in mice of the non-obese diabetic (NOD) strain 6-8 and gut microbiota differences in children that are associated with the development of T1D 9-11. Several studies have also described alterations to the gut mucosa in NOD mice and patients with T1D 12-16. Mucosal-associated invariant T cells (MAIT cells) are innate-like T cells that recognize bacterial metabolites derived from the synthesis of riboflavin and presented by the monomorphic major histocompatibility complex (MHC) class-I-related protein MR1 (refs. 17-19). These non-conventional T cells express a conserved αβ T cell antigen receptor (TCR) that consists of an invariant TCR α-chain (α-chain variable region 7.2 and α-chain joining regions 33, 20 and12 (V α 7.2-J α 33,20,12) in humans and V α 19-J α 33 in mice) with a restricted set of TCR β-chains. MAIT cells produce various cytokines, such as TNF, IFN-γ, IL-17 and granzyme B (GzB), that participate in tissue inflammation and cell death 17,20-28. The nearly complete absence of MAIT cells in germ-free mice 17,29 and their physiological localization at mucosal sites, including the gut 17,21 , suggest a strong interaction with the microbiota. Here we found alterations in MAIT cells in patients with T1D and, through the use of NOD mice, revealed a protective role for MAIT cells directed against T1D. The localization and function of MAIT cells highlight their key role in the maintenance of gut integrity whereby they control the development of autoimmune responses to pancreatic β-cells. RESULTS Alterations in MAIT cells in children with recent-onset T1D We first began our investigation of MAIT cells in T1D by analyzing the frequency and phenotype of MAIT cells in fresh peripheral Type 1 diabetes (T1D) is an autoimmune disease that results from the destruction of pancreatic b-cells by the immune system that involves innate and adaptive immune cells. Mucosal-associated invariant T cells (MAIT cells) are innate-like T-cells that recognize derivatives of precursors of bacterial riboflavin presented by the major histocompatibility complex (MHC) class I-related molecule MR1. Since T1D is associated with modification of the gut microbiota, we investigated MAIT cells in this pathology. In patients with T1D and mice of the non-obese diabetic (NOD) strain, we detected alterations in MAIT cells, including increased production of granzyme B, which occurred before the onset of diabetes. Analysis of NOD mice that were deficient in MR1, and therefore lacked MAIT cells, revealed a loss of gut integrity and increased anti-islet responses associated with exacerbated diabetes. Together our data highlight the role of MAIT cells in the maintenance of gut integrity and the control of anti-islet autoimmune responses. Monitoring of MAIT cells might represent a new biomarker of T1D, while manipulation of these cells might open new therapeutic strategies.

Published
2017
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64. Evaluation of power dissipation in a granular bed disturbed by an intruder a tool to design kneading operations

Author

Lehuen, Julien, Delenne, Jean-Yves, Sadoudi, Abdelkrim, Agnès, Duri, Ruiz, Thierry, Qualisud - Pôle de La Réunion (Qualisud Réunion ), Démarche intégrée pour l'obtention d'aliments de qualité (UMR QualiSud), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut de Recherche pour le Développement (IRD)-Avignon Université (AU)-Université de La Réunion (UR)-Université de Montpellier (UM)-Institut Agro - Montpellier SupAgro, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut de Recherche pour le Développement (IRD)-Avignon Université (AU)-Université de La Réunion (UR)-Université de Montpellier (UM)-Institut Agro - Montpellier SupAgro, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Ingénierie des Agro-polymères et Technologies Émergentes (UMR IATE), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Université de Montpellier (UM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro - Montpellier SupAgro, Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut de Recherche pour le Développement (IRD)-Avignon Université (AU)-Université de La Réunion (UR)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), and Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Institut National de la Recherche Agronomique (INRA)

Subjects
Ensiled granular medium, coarse graining method, DEM method, [SPI.GPROC]Engineering Sciences [physics]/Chemical and Process Engineering, [SPI.MECA]Engineering Sciences [physics]/Mechanics [physics.med-ph], ComputingMilieux_MISCELLANEOUS, Rheophysics
Abstract

International audience

Published
2021

66. Gut mucosa alterations and loss of segmented filamentous bacteria in type 1 diabetes are associated with inflammation rather than hyperglycaemia

Author

Rouland, Matthieu, primary, Beaudoin, Lucie, additional, Rouxel, Ophélie, additional, Bertrand, Léo, additional, Cagninacci, Lucie, additional, Saffarian, Azadeh, additional, Pedron, Thierry, additional, Gueddouri, Dalale, additional, Guilmeau, Sandra, additional, Burnol, Anne-Françoise, additional, Rachdi, Latif, additional, Tazi, Asmaa, additional, Mouriès, Juliette, additional, Rescigno, Maria, additional, Vergnolle, Nathalie, additional, Sansonetti, Philippe, additional, Christine Rogner, Ute, additional, and Lehuen, Agnès, additional

Published
2021
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68. NKT and Tolerance

Author

Diana, Julien, primary, Beaudoin, Lucie, additional, Gautron, Anne-Sophie, additional, and Lehuen, Agnès, additional

Published
2010
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72. Activation of natural killer T cells by [alpha]-galactosylceramide treatment prevents the onset and recurrence of autoimmune Type 1 diabetes

Author

Sharif, Shayan, Arreaza, Guillermo A., Zucker, Peter, Mi, Qing-Sheng, Sondhi, Jitin, Naidenko, Olga V., Kronenberg, Mitchell, Koezuka, Yasuhiko, Delovitch, Terry L., Gombert, Jean-Marc, Leite-de-Moraes, Maria, Gouarin, Christine, Zhu, Ren, Hameg, Agathe, Nakayama, Toshinori, Taniguchi, Masaru, Lepault, Francoise, Lehuen, Agnes, Bach, Jean-Francois, and Herbelin, Andre

Abstract

Type 1 diabetes (T1D) in non-obese diabetic (NOD) mice may be favored by immune dysregulation leading to the hyporesponsiveness of regulatory T cells and activation of effector T-helper type 1 (Th1) cells. The immunoregulatory activity of natural killer T (NKT) cells is well documented, and both interleukin (IL)-4 and IL-10 secreted by NKT cells have important roles in mediating this activity. NKT cells are less frequent and display deficient IL-4 responses in both NOD mice and individuals at risk for T1D (ref. 8), and this deficiency may lead to T1D (refs. 1,6-9). Thus, given that NKT cells respond to the [alpha]-galactosylceramide ([alpha]-GalCer) glycolipid in a CD1d-restricted manner by secretion of Th2 cytokines, we reasoned that activation of NKT cells by [alpha]-GalCer might prevent the onset and/or recurrence of T1D. Here we show that [alpha]-GalCer treatment, even when initiated after the onset of insulitis, protects female NOD mice from T1D and prolongs the survival of pancreatic islets transplanted into newly diabetic NOD mice. In addition, when administered after the onset of insulitis, [alpha]-GalCer and IL-7 displayed synergistic effects, possibly via the ability of IL-7 to render NKT cells fully responsive to [alpha]-GalCer. Protection from T1D by [alpha]-GalCer was associated with the suppression of both T- and B-cell autoimmunity to islet [beta] cells and with a polarized Th2-like response in spleen and pancreas of these mice. These findings raise the possibility that[alpha]-GalCer treatment might be used therapeutically to prevent the onset and recurrence of human T1D., Author(s): Shayan Sharif [1, 9]; Guillermo A. Arreaza [1, 9]; Peter Zucker [1, 9]; Qing-Sheng Mi [1, 9]; Jitin Sondhi [1, 9]; Olga V. Naidenko [2, 9]; Mitchell Kronenberg [2, [...]

Published
2001
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73. Outcome of SARS-CoV-2 infection linked to MAIT cell activation and cytotoxicity: evidence for an IL-18 dependent mechanism

Author

Flament, H., primary, Rouland, M., additional, Beaudoin, L., additional, Toubal, A., additional, Bertrand, L., additional, Lebourgeois, S., additional, Gouda, Z., additional, Rousseau, C., additional, Soulard, P., additional, Hurtado-Nedelec, M., additional, Luce, S., additional, Bailly, K., additional, Andrieu, M., additional, Boitard, C., additional, Vallet-Pichard, A., additional, Gautier, JF., additional, Ajzenberg, N., additional, Terrier, B., additional, Pene, F., additional, Ghosn, J., additional, Yazdanpanah, Y., additional, Visseaux, B., additional, Descamps, D., additional, Timsit, JF., additional, Monteiro, R.C., additional, and Lehuen, A., additional

Published
2020
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74. Mucosal-associated invariant T cells promote inflammation and intestinal dysbiosis leading to metabolic dysfunction during obesity

Author

Toubal, Amine, primary, Kiaf, Badr, additional, Beaudoin, Lucie, additional, Cagninacci, Lucie, additional, Rhimi, Moez, additional, Fruchet, Blandine, additional, da Silva, Jennifer, additional, Corbett, Alexandra J., additional, Simoni, Yannick, additional, Lantz, Olivier, additional, Rossjohn, Jamie, additional, McCluskey, James, additional, Lesnik, Philippe, additional, Maguin, Emmanuelle, additional, and Lehuen, Agnès, additional

Published
2020
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75. Mucosal-associated invariant T cells in autoimmune and immune-mediated diseases

Author

Agnès Lehuen, Ophélie Rouxel, 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), Laboratoire d'excellence Inflamex, Sorbonne Paris Cité, and Lehuen, Agnès

Subjects
0301 basic medicine, mediated-immune diseases, [SDV.IMM] Life Sciences [q-bio]/Immunology, Autoimmune diseases, Immunology, Inflammation, Mucosal associated invariant T cell, Biology, Mucosal-Associated Invariant T Cells, Proinflammatory cytokine, Pathogenesis, 03 medical and health sciences, Immune system, medicine, Immunology and Allergy, Animals, Humans, INSERM 1016, MAIT Cells, Cell Biology, 3. Good health, 030104 developmental biology, Immune System Diseases, mucosal-associated invariant T cells Correspondence Agn es Lehuen, inflammation, [SDV.IMM]Life Sciences [q-bio]/Immunology, medicine.symptom, innate T cells, Homing (hematopoietic), Tissue inflammation
Abstract

International audience; Autoimmune and inflammatory diseases have complex etiologies not fully understood. Both innate and adaptive immune cells are involved in the pathogenesis of these diseases. Mucosal-associated invariant T (MAIT) cells express an invariant TCRa chain (Va7.2-Ja33 in humans and Va19-Ja33 in mice) and recognize the conserved MHC-I-related molecule MR1 presenting bacterial metabolites derived from the synthesis of vitamin B. MAIT cells harbor tissue homing properties and produce inflammatory cytokines, suggesting that MAIT cells may play a key role in autoimmune and inflammatory diseases. In this review, we described the current knowledge on MAIT cells in these pathologies, based on patients analyses as well as mouse models. While most of the studies support a deleterious role of MAIT cells in tissue inflammation and destruction, a few reports suggest a protective role of MAIT cells. MAIT cells could represent a new biomarker of disease progression, and a better knowledge of their function might open new avenues for therapeutic strategies based on their manipulation.

Published
2018
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76. Mucosal-associated invariant T cells are a profibrogenic immune cell population in the liver

Author

Hegde, Pushpa, Weiss, Emmanuel, Paradis, Valérie, Wan, Jinghong, Mabire, Morgane, Sukriti, Sukriti, Rautou, Pierre-Emmanuel, Albuquerque, Miguel, Picq, Olivia, Gupta, Abhishak Chandra, Ferrere, Gladys, Gilgenkrantz, Hélène, Kiaf, Badr, Toubal, Amine, Beaudoin, Lucie, Lettéron, Philippe, Moreau, Richard, Lehuen, Agnès, Lotersztajn, Sophie, Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Excellence Inflamex [Paris] (Faculté de Médecine Xavier Bichat), Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (COMUE) (USPC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Département d'Anesthésie et Réanimation [Hôpital Beaujon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département de Pathologie [Hôpital Beaujon], Service d'hépatologie [Hôpital Beaujon], Institut Cochin (IC UM3 (UMR 8104 / U1016)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Lehuen, Agnès

Subjects
Adult, Liver Cirrhosis, Male, [SDV.IMM] Life Sciences [q-bio]/Immunology, Macrophages, Science, Cell Count, Middle Aged, Article, Coculture Techniques, Mucosal-Associated Invariant T Cells, Mice, Liver, Non-alcoholic Fatty Liver Disease, Animals, Humans, [SDV.IMM]Life Sciences [q-bio]/Immunology, lcsh:Q, Female, lcsh:Science, Cells, Cultured, Aged
Abstract

Liver fibrosis is the common response to chronic liver injury, and leads to cirrhosis and its complications. Persistent inflammation is a driving force of liver fibrosis progression. Mucosal-associated invariant T (MAIT) cells are non-conventional T cells that display altered functions during chronic inflammatory diseases. Here, we show that circulating MAIT cells are reduced in patients with alcoholic or non-alcoholic fatty liver disease-related cirrhosis while they accumulate in liver fibrotic septa. Using two models of chronic liver injury, we demonstrate that MAIT cell-enriched mice show increased liver fibrosis and accumulation of hepatic fibrogenic cells, whereas MAIT cell-deficient mice are resistant. Co-culture experiments indicate that MAIT cells enhance the proinflammatory properties of monocyte-derived macrophages, and promote mitogenic and proinflammatory functions of fibrogenic cells, via distinct mechanisms. Our results highlight the profibrogenic functions of MAIT cells and suggest that targeting MAIT cells may constitute an attractive antifibrogenic strategy during chronic liver injury., Hepatic fibrosis represents the liver response to chronic injury and can lead to cirrhosis. Here the authors show that mucosal-associated invariant T cells mediate chronic inflammation and fibrogenesis in the liver by inducing a proinflammatory phenotype in macrophages and myofibroblasts and proliferation of the latter.

Published
2018
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77. Gut mucosa alterations and loss of segmented filamentous bacteria in type 1 diabetes are associated with inflammation rather than hyperglycaemia.

Author

Rouland, Matthieu, Beaudoin, Lucie, Rouxel, Ophélie, Bertrand, Léo, Cagninacci, Lucie, Saffarian, Azadeh, Pedron, Thierry, Gueddouri, Dalale, Guilmeau, Sandra, Burnol, Anne-Françoise, Rachdi, Latif, Tazi, Asmaa, Mouriès, Juliette, Rescigno, Maria, Vergnolle, Nathalie, Sansonetti, Philippe, Rogner, Ute Christine, and Lehuen, Agnès

Subjects
TYPE 1 diabetes, AEROBIC bacteria, FILAMENTOUS bacteria, HYPERGLYCEMIA, ELEMENTAL diet, MATRIX-assisted laser desorption-ionization, EPICATECHIN
Published
2022
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78. Expérimentations et simulations numériques pour quantifier l'influence d'une pâle lors de l'opération de malaxage de milieux granulaires

Author

Lehuen, Julien, Delenne, Jean-Yves, Sadoudi, Abdelkrim, Cassan, Denis, Duri, Agnès, Ruiz, Thierry, Ingénierie des Agro-polymères et Technologies Émergentes (UMR IATE), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université Montpellier 2 - Sciences et Techniques (UM2), Démarche intégrée pour l'obtention d'aliments de qualité (UMR Qualisud), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Université de La Réunion (UR)-Université de Montpellier (UM)-Avignon Université (AU)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Montpellier 1 (UM1), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Qualisud - Pôle de La Réunion (Qualisud Réunion), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Avignon Université (AU)-Université de La Réunion (UR)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Avignon Université (AU)-Université de La Réunion (UR)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), and Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Institut National de la Recherche Agronomique (INRA)

Subjects
PIV, DEM simulation, Milieu granulaire ensilé, [SPI.GPROC]Engineering Sciences [physics]/Chemical and Process Engineering, [PHYS.MECA]Physics [physics]/Mechanics [physics], [SPI.MECA]Engineering Sciences [physics]/Mechanics [physics.med-ph], Rhéophysique, ComputingMilieux_MISCELLANEOUS
Abstract

International audience; 1. IntroductionL'étude de la transmission des contrainteset des typologies de mouvements dans un lit de poudre dans des conditions de faible cisaillement constitue un défi pour contrôler les procédésimpliquant la mobilité des particules, tels que lemalaxage ou encore l'agglomération (Fig. 1 a) [1]. Ce travail porte sur la quantificationde la capacité d'un intrudeur à transmettrela mobilité des particules dans un lit granulaire[2].L’approche suivie repose sur l’analyseconjointed’une expérimentation spécifique et le développement decodesde calcul DEM (Discrete Element Method) [3]. L’expériencedéveloppéepermet (i) de visualiser la mobilitédes particules au voisinage d’un intrudeuret (ii) de mesurer la force de traînée perçue lors de son mouvement dans lemilieu granulaire ensilé. Afin d'identifier la propagation deseffortsdans le lit de particules, expérimentationset simulations numériquessont comparées pourdifférentes vitesses de l’intrudeur.2. MéthodesDispositif expérimental. Le montage expérimental (Fig. 1 b) comprendune cellulesemi-ouverteconstituéede parois transparentespermettant l’emploi d’une caméra à images rapides puis dont les analyses par analyse PIV(Particle Image Velocimetry) fournissent le champ de déplacement des particules (billes de verre de 1-2 mm de diamètre) au voisinage de l’intrudeur (Fig. 1 c). L’intrudeur en acier est relié à un capteur de force. Il est insérédans la cellulepuis le lit de particules est mis en place. L’intrudeur est ensuite retirédu milieugranulaireparun mouvement vertical ascendant. La force de traînée et le champ de vitesses induits sontalors mesurés.Simulation numérique. Un code en c++a été spécifiquement développé pour calculer les déplacements et l’évolution duréseau de forces intergranulaires (forces normales, tangentielleset moments) au sein dumilieu ensilé (Fig. 1d). L’utilisation d’un«coarse graining» permet d’accéder auchamp de contraintes. Une méthode originale de «doublegrille» est développée afind’augmenter la précisiondes calculs et de calculerle champ de compacité. Ces trois codes, autorisentl’exploration de tous les contacts entre les particules à chaque instant fournissantune visualisationde l’influence de l’intrudeursur la microstructure.3. Résultats et discussionLes mesures de force et des champs de déplacement des particulespermettent d’identifier différentes typologiesde mobilités (compactage, chargement/rupture des chaînes de forces, effondrements latéraux, avalanches, etc.). Les résultats expérimentauxsont comparésaux simulations de DEMqui renseignentsur l'évolution microstructurelle du milieu (compacité, durée de vie des contacts, shear-banding(Fig. 1 e)...). Les fluctuations de la contrainte sur l’intrudeur sont cycliques et correspondentaux chargementsetrupturesdes chaînes de forces dans la zone de particules influencées. Leur dépendance en fonction des conditions opératoires est explicitée. L’analyse des corrélations spatio-temporelles duchamps de vitesse permet de définir laportée de l’intrudeurcommeune longueur caractéristique liée au développement de gradients de mobilités.4. ConclusionLes observations expérimentales couplées auxsimulations de DEM permettent d'accéder au comportement du milieu granulaireà l'échelle du réacteur et à l'échelle de sa microstruture. L'analyse de l'évolution du réseau de forces intergranulairespermet de définir deslongueurs et temps caractéristiques à partir denombres dimensionnels. Ces paramètres peuvent ensuite être utilisés pour optimiser la conduite d'un procédéimpliquant la mobilité des particules induite par unapport d'énergie mécanique externe telle qu’unintrudeur.

Published
2019

79. Experimental and numerical analyses by DEM of the range of a probe in a granular medium

Author

Lehuen, Julien, Delenne, Jean-Yves, Sadoudi, Abdelkrim, Cassan, Denis, Duri, Agnès, Ruiz, Thierry, Ingénierie des Agro-polymères et Technologies Émergentes (UMR IATE), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Qualisud - Pôle de La Réunion (Qualisud Réunion), Démarche intégrée pour l'obtention d'aliments de qualité (UMR Qualisud), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Avignon Université (AU)-Université de La Réunion (UR)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Avignon Université (AU)-Université de La Réunion (UR)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Institut National de la Recherche Agronomique (INRA), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université Montpellier 2 - Sciences et Techniques (UM2), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), and Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Université de La Réunion (UR)-Université de Montpellier (UM)-Avignon Université (AU)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Montpellier 1 (UM1)

Subjects
Ensiled granular medium, DEM Method, [SPI.GPROC]Engineering Sciences [physics]/Chemical and Process Engineering, [PHYS.MECA]Physics [physics]/Mechanics [physics], [SPI.MECA]Engineering Sciences [physics]/Mechanics [physics.med-ph], Rheophysics
Abstract

International audience; Highlights • There is vertical stratification within a granular medium located in a reactor. • The range of force imposed by the blade is all the lower when the speed is high. • DEM simulations give the structural rearrangement which occurs during trials. • Spatiotemporal correlations of particle motions observed by PIV could be explained by DEM.

Published
2019

80. Study of slip threshold at the contact's scale in a static granular column

Author

Lehuen, Julien, Delenne, Jean-Yves, Sadoudi, Abdelkrim, Cassan, Denis, Ruiz, Thierry, Duri, Agnès, Ingénierie des Agro-polymères et Technologies Émergentes (UMR IATE), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Démarche intégrée pour l'obtention d'aliments de qualité (UMR Qualisud), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Avignon Université (AU)-Université de La Réunion (UR)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université Montpellier 2 - Sciences et Techniques (UM2), Qualisud - Pôle de La Réunion (Qualisud Réunion), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Université de La Réunion (UR)-Université de Montpellier (UM)-Avignon Université (AU)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Montpellier 1 (UM1)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Université de La Réunion (UR)-Université de Montpellier (UM)-Avignon Université (AU)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Montpellier 1 (UM1), and Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro)

Subjects
Ensiled granular medium, slip threshold, Coarse graining, DEM, [SPI.GPROC]Engineering Sciences [physics]/Chemical and Process Engineering, [PHYS.MECA]Physics [physics]/Mechanics [physics], [SPI.MECA]Engineering Sciences [physics]/Mechanics [physics.med-ph], ComputingMilieux_MISCELLANEOUS, Rheophysics, static granular column
Abstract

International audience; The mechanical equilibrium of an ensiled grain column depends on mechanical and geometrical parameters related to the grains on the one hand and to the configuration of the silo on the other hand, but also to the implementation conditions (flow rate, height of fall…). The observed equilibrium at the silo scale is the result of the local equilibria achieved at the particle scale, a scale at which we observe a strong dependence on the history of the intergranular contact establishment. The microstructural analysis of such a system allows to better understand and control the storage of materials (powders, cements, waste) in long-term conditions (silo, bag) or in shorter-term conditions (conveying, maritime and road transport). In order to understand the slope of the stress profiles, experiments and Discrete Element Method (DEM) simulations are compared to investigate the structure of an ensiled granular medium poured in a cell by a single point source and different flow rates (parameters which allow to control the kinetic energy of the grains). A population of glass beads of 1 to 2 mm (50/50 in volume) diameter with a small span value is poured in an open glass cell container made of transparent glass walls. A flat steel probe, linked to a load cell of a texture analyser which is used as a force sensor, is used to simulate the bottom of the cell and to measure the applied vertical stress. The filling is provided by a funnel and the flow rate is modulated by the output diameter. A code in c ++ , using both DEM and coarse graining method (Weinhart and Luding, 2016), is developed to calculate the force network, stress and compactness fields of a similar ensiled granular medium under gravity. With this code, all the contacts between the particles are obtained by calculating (i) the normal and tangential forces, (ii) the moment, and (iii) the mobility of each particle. Experiments show that the vertical stress profile depends on the pouring rate which confirms the importance of contact history. After each filling conditions, the slipping threshold is not obtained for all grains located on the walls of the cell. In order to activate the contacts between walls and grains, a small translation of the bottom wall is achieved. After this motion, a proportion of contacts at slip threshold is established from the bottom until a length which defines the perturbed zone located around the wall translated. The apparent weight of the granular column decreases of the contribution of the weight of this zone. Activation of the contacts seem to amplified such a phenomenon. Thus the behavior inside large silo can be reproduced at a tinnier scale defined by the scope of the slip threshold. DEM simulations show that in all tested cases, the compactness is relatively uniform, this contact activation is only lightening the vertical force network and allows let preferential contact network percolating from a wall to the other opposite one. This observation

Published
2019

81. Experimental and numerical studies of semi-confined heap structure after variable pouring conditions

Author

Lehuen, Julien, Delenne, Jean-Yves, Sadoudi, Abdelkrim, Cassan, Denis, Planchot, Veronique, Ruiz, Thierry, Duri, Agnès, Ingénierie des Agro-polymères et Technologies Émergentes (UMR IATE), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Institut National de la Recherche Agronomique (INRA), Département Caractérisation et Elaboration des Produits Issus de l'Agriculture (CEPIA), Institut National de la Recherche Agronomique (INRA), Qualisud - Pôle de La Réunion (Qualisud Réunion), Démarche intégrée pour l'obtention d'aliments de qualité (UMR Qualisud), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Avignon Université (AU)-Université de La Réunion (UR)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Avignon Université (AU)-Université de La Réunion (UR)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), and Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)

Subjects
Ensiled granular medium, DEM Method, forces network, [SPI.FLUID]Engineering Sciences [physics]/Reactive fluid environment, coarse-graining, Janssen effect, homemade code, [SPI.GPROC]Engineering Sciences [physics]/Chemical and Process Engineering, [PHYS.MECA]Physics [physics]/Mechanics [physics], [SPI.MECA]Engineering Sciences [physics]/Mechanics [physics.med-ph], Rheophysics, ComputingMilieux_MISCELLANEOUS, [SPI.MAT]Engineering Sciences [physics]/Materials
Abstract

International audience; The classic experience of filling a container with a granular medium poured froma source point reveals the presence of the intergranular forces network by themanifestation of the Janssen effect (Janssen, 1895). Indeed, the measurement ofthe stress applied at the base of the container according to the bed particleheight, shows that the static mechanical state of the ensiled granular medium isnot comparable to a hydrostatic one which is characteristic of a fluid. The lateraldeflection of gravity forces to the walls via the network of intergranular contacts,allows to explain the lowering of vertical stress (σzz) in relation to hydrostaticpressure. Moreover, the sliding threshold condition must be established at thewalls to explain the "saturant" shape of the σzz profile (Ovarlez and Clément,2005). If mechanical properties are involved to explain this apparentphenomenon understanding as a static equilibrium, the analyze of the free surfaceduring pouring correlated to the local mechanical state allow to indicate thatkinetic energy had an influence on the Janssen effect (Mandato et al. 2012; Duri etal. 2018). In order to revisit the Janssen effect, experiments and Discrete ElementMethod (DEM) simulations are compared to investigate the structure of an ensiledgranular medium poured in a cell by a single point at different initial drop heightsand flow rate (parameters which allow to control kinetic energy).Experimental device. The granular medium consists of a population of glass beadsof 1 to 2 mm diameter with a small span value (50/50 in volume). The experimentalset-up, developed in Mandato et al. (2012), consists of an open glass cell container(51 x 100 x 160 mm) made of transparent glass walls. A flat and rectangular steelprobe is especially designed to fit into the glass container. A small probe allowslocal measurements of the vertical stress in the powder bed. A large probe is usedto simulate the bottom of the cell and allows a global measurement of the verticalstress, as in Janssenʼs experiment (Janssen, 1895). Whatever its width, the probeis screwed on a rod that is linked to a load cell of a texture analyser (TA.XT2, TableMicro System), which is used as a force sensor. The filling is provided by a funneland the flow rate is modulated by the output diameter. After pouring, the slopeangle and the arrow of the free surface are measured by image analysis.Numerical simulation. We develop our own homemade code in c++using the DEM.Then we decide to develop also a code using the coarse-graining method(Weinhart and Luding, 2016) to highlight on the different fields. This last methodwhich doesnʼt give access to the compactness near the wall, is replaced by a newmethod using two grids in order to increase the accurate. With these three codes we can now explore all the contacts between the particles by the calculus of (i)normal and tangential forces, (ii) moment, (iii) mobility, of each particle.Results. The variation of the initial drop height and the flow rate impacts the slopeof the free surface: crater form in high kinetic energy conditions, heap form inlowest conditions and intermediary slopes between these conditions (from plate to“camel-like” form). The measured and calculated values of the arrow and of theangle of repose are in very good agreement in each case. Experiments andnumerical simulation highlight the same layout of the vertical stress field (Fig. 1). Inthe upper part of the particle bed, there is a layer in which the stress is generallyassimilated to a “quasi-hydrostatic” state. It can be seen that under this first layer,Janssenʼs hypothesis that stresses are lateral uniformity is not valid: there is astrong local heterogeneity of the stress within the granular medium. It can be seenthat the redirection coefficient defined by Janssen (Janssen, 1985) ratio betweenlateral stress and vertical stress, is not constant. The study of thickness and meanstress in each different zone of the bed versus kinetic energy during the fillingstage had been realized. The static mechanical state of the particle bed is also dueto this dynamical parameter and this point is usually not taking into account.

Published
2019

82. Mucosal-associated invariant T cells and disease

Author

Agnès Lehuen, Isabelle Nel, Sophie Lotersztajn, and Amine Toubal

Subjects
0301 basic medicine, Vitamin b, History, Cell, Apoptosis, Mucosal associated invariant T cell, Disease, Biology, Infections, Mucosal-Associated Invariant T Cells, Education, Minor Histocompatibility Antigens, 03 medical and health sciences, 0302 clinical medicine, Neoplasms, medicine, Humans, Inflammation, Histocompatibility Antigens Class I, Interleukin-17, Tissue migration, Acquired immune system, 3. Good health, Computer Science Applications, 030104 developmental biology, medicine.anatomical_structure, Immunology, Function (biology), 030215 immunology
Abstract

Mucosal-associated invariant T (MAIT) cells are unique innate-like T cells that bridge innate and adaptive immunity. They are activated by conserved bacterial ligands derived from vitamin B biosynthesis and have important roles in defence against bacterial and viral infections. However, they can also have various deleterious and protective functions in autoimmune, inflammatory and metabolic diseases. MAIT cell involvement in a large spectrum of pathological conditions makes them attractive targets for potential therapeutic approaches. Mucosal-associated invariant T cells display innate, effector-like qualities and are involved, in various ways, in infectious and non-infectious diseases. Insights into their activation, tissue migration and function are revealing their beneficial and deleterious roles in disease.

Published
2019

83. Janssen's effect in a granular cell revisited by experiments and numerical simulations

Author

Lehuen, Julien, Delenne, Jean-Yves, Sadoudi, Abdelkrim, Cassan, Denis, Duri, Agnès, Ruiz, Thierry, Ingénierie des Agro-polymères et Technologies Émergentes (UMR IATE), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Qualisud - Pôle de La Réunion (Qualisud Réunion), Démarche intégrée pour l'obtention d'aliments de qualité (UMR Qualisud), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Avignon Université (AU)-Université de La Réunion (UR)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Avignon Université (AU)-Université de La Réunion (UR)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Institut National de la Recherche Agronomique (INRA), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université Montpellier 2 - Sciences et Techniques (UM2), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), and Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Université de La Réunion (UR)-Université de Montpellier (UM)-Avignon Université (AU)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Montpellier 1 (UM1)

Subjects
Janssen effect, [PHYS.MECA]Physics [physics]/Mechanics [physics], Centre international d´études supérieures en sciences agronomiques, Granular matter, [SPI.MECA]Engineering Sciences [physics]/Mechanics [physics.med-ph], international d´études supérieures en sciences agronomiques, ensiled granular medium, coarse graining, DEM simulation, Centre international d'études supérieures en sciences agronomiques -France, [SPI.GPROC]Engineering Sciences [physics]/Chemical and Process Engineering, Discrete Element Method, Université Montpellier 2 -Sciences et Techniques, Université Montpellier 1, Rheophysics
Abstract

International audience; The classic experience of filling a container with a granular medium poured from a source point reveals the presence of the intergranular force network by the manifestation of the Janssen effect (Janssen, 1895). Indeed, the measurement of the stress applied at the base of the container according to the bed particle height, shows that the static mechanical state of the ensiled granular medium is characterized by the lateral deflection of gravity forces to the walls via the network of intergranular contacts. In order to model this difference from a hydrostatic state, Janssen (1895) purposed to integrate all along the cell, the stress balance established at a layer scale. This equation universally used, is defined with three major hypotheses: (i) lateral uniformity of the vertical stress in each layer, (ii) the lateral stress is still proportional to the vertical stress (definition of the redirection coefficient), and (iii) the sliding threshold condition at the walls. With these assumptions the model describes the experimental profile of the vertical stress with its particular "saturant" slope (Ovarlez and Clément, 2005). If mechanical properties are involved to explain this apparent phenomenon understood as a static equilibrium, the free surface analysis during pouring correlated to the local mechanical state allows to indicate that kinetic energy has an influence on the Janssen effect (Duri et al. 2018). In order to revisit the Janssen effect, experiments and Discrete Element Method (DEM) simulations are compared to investigate the structure of an ensiled granular medium poured in a cell by a single point at different initial drop heights and flow rates (parameters which allow to control kinetic energy). A population of glass beads of 1 to 2 mm diameter with a small span value (50/50 in volume) is poured in an open glass cell container made of transparent glass walls. A flat steel probe is used to simulate the bottom of the cell and allows the measurement of the applied vertical stress, as in Janssen's experiment (Janssen, 1895). The probe is screwed on a rod that is linked to a load cell of a texture analyser (TA.XT2, Table Micro System), which is used as a force sensor. The filling is provided by a funnel and the flow rate is modulated by the output diameter.

Published
2019

84. 1190-P: IFN-Alpha Kinoid: A Promising Vaccine against Type 1 Diabetes Targeting IFN-alpha in NOD Mice

Author

Fabien Colaone, Géraldine Grouard-Vogel, Samir Hamdi, Jennifer Da Silva, Agnès Lehuen, Noémie Caillot, Romain Bertrand, Boitard F. Boitard, and Jonathan Bonnefoy

Subjects
biology, business.industry, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Nod, Active immunization, medicine.disease, Immunization, Polyclonal antibodies, Immunology, Internal Medicine, medicine, biology.protein, business, Adjuvant, Insulitis, Keyhole limpet hemocyanin, NOD mice
Abstract

Major elements highlight IFNα implication in type 1 diabetes (T1D) pathogenesis. While there is still no cure for this autoimmune disease, we aimed to evaluate the benefit of IFNα kinoid (IFN-K). This conjugated vaccine consisting of IFNα coupled to Keyhole limpet hemocyanin as a carrier protein elicits the production of polyclonal anti-IFNα neutralizing antibodies and has shown beneficial effects in a recent phase IIb trial in lupus (NCT02665364). Three independent experiments in NOD mice were performed to evaluate the activity of anti-IFNα neutralizing antibodies, conveyed either by maternal transfer or by passive or active immunization. Glycemia was monitored by a glucometer, neutralizing antibodies by the virus-induced cytopathic effect assay and H&E pancreas sections were evaluated in blind. In the first study, we compared T1D incidence in offsprings from IFN-K or KLH immunized mothers with sentinels. In the second study, mice were passively immunized with purified total IgG from sera collected in NOD mice immunized with IFN-K or KLH. Finally, active immunization was performed with IFN-K, KLH or PBS in combination with a squalene oil-in-water adjuvant. Mice were immunized at 5, 10 or 15 weeks of age. Anti-IFNα neutralizing antibodies were effectively conveyed from mothers to offspring, and levels decreased over time to completely disappear by month 3. In progeny from IFN-K immunized mice, despite transient and low amount of neutralizing antibodies, insulitis was decreased compared to control groups and T1D onset was delayed. In the second study, long-lasting administrations of total IgG comprising anti-IFNα neutralizing antibodies conferred protection towards T1D development, while total IgG from KLH-immunized mice did not. Finally, diabetes incidence was reduced when IFN K immunization started at week 10 of age. These different elements point out the need to neutralize IFNα during NOD lifetime to prevent T1D, and encourage us to evaluate IFN-K in newly diagnosed T1D patients. Disclosure N. Caillot: None. F. Colaone: None. R. Bertrand: None. J. Da Silva: None. S. Hamdi: None. J. Bonnefoy: None. A. Lehuen: Board Member; Spouse/Partner; Inatheris. Consultant; Self; Neovacs. B.F. Boitard: None. G. Grouard-Vogel: None.

Published
2019
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87. Mucosal-associated invariant T cells promote inflammation and intestinal dysbiosis leading to metabolic dysfunction during obesity

Author

Toubal, A, Kiaf, B, Beaudoin, L, Cagninacci, L, Rhimi, M, Fruchet, B, da Silva, J, Corbett, AJ, Simoni, Y, Lantz, O, Rossjohn, J, McCluskey, J, Lesnik, P, Maguin, E, Lehuen, A, Toubal, A, Kiaf, B, Beaudoin, L, Cagninacci, L, Rhimi, M, Fruchet, B, da Silva, J, Corbett, AJ, Simoni, Y, Lantz, O, Rossjohn, J, McCluskey, J, Lesnik, P, Maguin, E, and Lehuen, A

Abstract

Obesity is associated with low-grade chronic inflammation promoting insulin-resistance and diabetes. Gut microbiota dysbiosis is a consequence as well as a driver of obesity and diabetes. Mucosal-associated invariant T cells (MAIT) are innate-like T cells expressing a semi-invariant T cell receptor restricted to the non-classical MHC class I molecule MR1 presenting bacterial ligands. Here we show that during obesity MAIT cells promote inflammation in both adipose tissue and ileum, leading to insulin resistance and impaired glucose and lipid metabolism. MAIT cells act in adipose tissue by inducing M1 macrophage polarization in an MR1-dependent manner and in the gut by inducing microbiota dysbiosis and loss of gut integrity. Both MAIT cell-induced tissue alterations contribute to metabolic dysfunction. Treatment with MAIT cell inhibitory ligand demonstrates its potential as a strategy against inflammation, dysbiosis and metabolic disorders.

Published
2020

90. Mucosal-associated invariant T (MAIT) cells are depleted and prone to apoptosis in cardiometabolic disorders

Author

Karen E. Assmann, Richard Isnard, Agnès Lehuen, Sothea Touch, Christine Rouault, Christine Poitou, Florian Marquet, Héléna Mosbah, Judith Aron-Wisnewsky, Sébastien André, Karine Clément, Magali Fradet, Gérard Helft, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), 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), This work was supported by Agence Nationale de la Recherche (ANR OB-MAIT) and the European Union’s Seventh Framework Program for research, technological development, and demonstration under grant agreement HEALTH-F4-2012-305312 (MetaCardis). Assistance Publique–Hôpitaux de Paris is the promoter of the clinical investigation. The authors also thank Société Française de Nutrition (SFN), Fondation Coeur et Artères, and F-CRIN-FORCE network for support., MetaCardis Consortium : Oppert JM, Khémis J, Cassuto D, Ciangura C, Vatier C, Andreelli F, Bosquet F, Jacqueminet S, Hartemann A, Amouyal C, Salem JE, Bourron O, Giral P, Montalescot G, Barthelemy O, Sylvain J, Pousset F, Hulot JS, Kerneis M, Boubrit L, Petroni T, Bastard JP, Fellahi S., European Project: 305312,EC:FP7:HEALTH,FP7-HEALTH-2012-INNOVATION-1,METACARDIS(2012), Lehuen, Agnès, Metagenomics in Cardiometabolic Diseases - METACARDIS - - EC:FP7:HEALTH2012-11-01 - 2017-10-31 - 305312 - VALID, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre National de la Recherche Scientifique (CNRS)-Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), and Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
0301 basic medicine, lymphocytes, [SDV.IMM] Life Sciences [q-bio]/Immunology, Cell, Inflammation, Biochemistry, Coronary artery disease, 03 medical and health sciences, Antigen, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Genetics, medicine, Molecular Biology, business.industry, Type 2 Diabetes Mellitus, medicine.disease, 3. Good health, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 030104 developmental biology, medicine.anatomical_structure, Apoptosis, inflammation, Heart failure, cardiology, Immunology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Metabolic syndrome, medicine.symptom, business, metabolism, Biotechnology
Abstract

The disruption of systemic immune homeostasis is a key mediator in the progression of cardiometabolic diseases (CMDs). We aimed to extend knowledge regarding the clinical relevance of CMD-associated variation of circulating mucosal-associated invariant T (MAIT) cell abundance and to explore underlying cellular mechanisms. We analyzed cross-sectional data from 439 participants of the Metagenomics in Cardiometabolic Diseases (MetaCardis) study, stratified into 6 groups: healthy control subjects and patients with metabolic syndrome (MS), obesity, type 2 diabetes mellitus (T2DM), and coronary artery disease (CAD) without, or with congestive heart failure (CAD-CHF). Blood MAIT cell frequency was significantly decreased in all CMD groups, including early (MS) and later (CAD and CAD-CHF) stages of disease progression. Reduced MAIT cell abundance was associated with increased glycosylated hemoglobin, inflammation markers, and deterioration of cardiac function. Glucose dose dependently promoted MAIT cell apoptosis in vitro, independently of anti-CD3 and cytokine-mediated activation. This outcome suggests the prominence of metabolic over an antigenic or cytokine-rich environment to promote MAIT cell reduction in patients with CMD. In summary, all stages of CMDs are characterized by reduced circulating MAIT cells. Chronically elevated blood glucose levels could contribute to this decline. These data extend the pathologic relevance of MAIT cell loss and suggest that MAIT cell abundance may serve as an indicator of cardiometabolic health.-Touch, S., Assmann, K. E., Aron-Wisnewsky, J., Marquet, F., Rouault, C., Fradet, M., Mosbah, H., MetaCardis Consortium, Isnard, R., Helft, G., Lehuen, A., Poitou, C., Clement, K., Andre, S. Mucosal-associated invariant T (MAIT) cells are depleted and prone to apoptosis in cardiometabolic disorders.

Published
2018
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93. Granular flow and drag force around an intruder: experimental and numerical observations

Author

Lehuen, Julien, Delenne, Jean-Yves, Ruiz, Thierry, Duri, Agnès, Ingénierie des Agro-polymères et Technologies Émergentes (UMR IATE), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université Montpellier 2 - Sciences et Techniques (UM2), Démarche intégrée pour l'obtention d'aliments de qualité (UMR Qualisud), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Université de La Réunion (UR)-Université de Montpellier (UM)-Avignon Université (AU)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Montpellier 1 (UM1), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Institut National de la Recherche Agronomique (INRA), Qualisud - Pôle de La Réunion (Qualisud Réunion), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Avignon Université (AU)-Université de La Réunion (UR)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Avignon Université (AU)-Université de La Réunion (UR)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), and Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)

Subjects
Ensiled granular medium, rheophysic of granular media, intruder, Ensiled granular media, DEM method, [PHYS.MECA]Physics [physics]/Mechanics [physics], [SPI.MECA]Engineering Sciences [physics]/Mechanics [physics.med-ph], local force, Particle flow, PIV, Physics::Fluid Dynamics, [SPI.GPROC]Engineering Sciences [physics]/Chemical and Process Engineering, discrete element method, Rheophysics, Computer Science::Cryptography and Security
Abstract

International audience; By means of quasi-2D experiments and 2D numerical tests we investigate the particle flow around a moving intruder immersed into an ensiled granular material. The intruder (a blade) is first positioned at the bottom of a transparent box. The box is filled with glass beads up to a fixed bed height. The intruder is then moved upward at constant velocity. The flow around the intruder is analyzed using a Particle Image Velocimetry (PIV) method, while a force sensor monitors the exerted vertical drag force. In the vicinity of the intruder, avalanches, lateral collapsing, compacted zones, shear banding… are clearly observed. These flow typologies are correlated to successive loading-unloading events in the force signal. As a function of the intruder depth, three flow regimes of the particles can be distinguished: quasistatic, frictional and collisional. Regarding to numerical simulations, a Discrete Element (DEM) approach was developed to clarify the force transmission at the scale of the contact between particles and with the intruder. Specific boundaries conditions were programed to simulate the geometry of the experimental device, with different sizes of boxes and intruders shapes. The grain flow and the forces acting on the intruder are computed during its ascending motion. Finally, both experimental and numerical parametric study were performed, in which the velocity of the intruder was varied. Based on these results the experimental and numerical flow regimes are compared and analyzed according to the force networks obtained by the DEM.

Published
2018

94. [Mucosal-associated invariant T cells]

Author

Ophélie, Rouxel and Agnès, Lehuen

Subjects
Intestines, Diabetes Mellitus, Type 1, Insulin-Secreting Cells, Animals, Humans, Biomarkers, Mucosal-Associated Invariant T Cells
Published
2018

95. Drag force applied to an intruder during its extraction from an ensiled granular medium: experiments and 2D DEM simulations

Author

Lehuen, Julien, Delenne, Jean-Yves, Ruiz, Thierry, Duri, Agnès, Ingénierie des Agro-polymères et Technologies Émergentes (UMR IATE), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Qualisud - Pôle de La Réunion (Qualisud Réunion), Démarche intégrée pour l'obtention d'aliments de qualité (UMR Qualisud), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Avignon Université (AU)-Université de La Réunion (UR)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Avignon Université (AU)-Université de La Réunion (UR)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Institut National de la Recherche Agronomique (INRA), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université Montpellier 2 - Sciences et Techniques (UM2), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), and Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Université de La Réunion (UR)-Université de Montpellier (UM)-Avignon Université (AU)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Montpellier 1 (UM1)

Subjects
Physics::Fluid Dynamics, PIV, Ensiled granular medium, DEM Method, Rheophysic of granular medium, [SPI.GPROC]Engineering Sciences [physics]/Chemical and Process Engineering, [PHYS.MECA]Physics [physics]/Mechanics [physics], Discrete Element Method, Intruder, [SPI.MECA]Engineering Sciences [physics]/Mechanics [physics.med-ph], Particle flow, Rheophysics, Drag force
Abstract

International audience; In many powder technologies such as kneading, mixing or raking, an intruder is used to shear the granular material and to induce particle mobilities. For such processes, it is important to better control the energy transfert from the reactor to the particle scale. In this work we investigate, by means of experiments and Discrete Element Method (DEM) simulations, the drag force acting on an intruder vertically pulled up from an ensiled granular medium. In the experiments, the intruder is first positioned at the bottom of a cell filled with glass beads and then moved upward at constant velocity. The fluctuations of the drag force acting on the moving intruder is monitored by a force sensor while the particle flow around it is captured using a high-speed camera. The images are then processed using a Particle Image Velocimetry (PIV) code. The force profiles and the flow of particles around the intruder are characterized as a function of the intruder velocity. A 2D DEM code was developed in order to simulate this problem with similar boundary conditions. With this code, it is possible to better analyzed the perturbation of the granular network in the vicinity of the intruder. The simulated particle flows and the drag force show a good agreement with the experimental results. Three flow regimes can be distinguished depending on the depth of the intruder: quasistatic, frictional and collisional. These regimes depend to the velocity of the intruder scaled by the characteristic particle speed () of the particles.

Published
2018

96. Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition)

Author

Cossarizza, Andrea, primary, Chang, Hyun‐Dong, additional, Radbruch, Andreas, additional, Acs, Andreas, additional, Adam, Dieter, additional, Adam‐Klages, Sabine, additional, Agace, William W., additional, Aghaeepour, Nima, additional, Akdis, Mübeccel, additional, Allez, Matthieu, additional, Almeida, Larissa Nogueira, additional, Alvisi, Giorgia, additional, Anderson, Graham, additional, Andrä, Immanuel, additional, Annunziato, Francesco, additional, Anselmo, Achille, additional, Bacher, Petra, additional, Baldari, Cosima T., additional, Bari, Sudipto, additional, Barnaba, Vincenzo, additional, Barros‐Martins, Joana, additional, Battistini, Luca, additional, Bauer, Wolfgang, additional, Baumgart, Sabine, additional, Baumgarth, Nicole, additional, Baumjohann, Dirk, additional, Baying, Bianka, additional, Bebawy, Mary, additional, Becher, Burkhard, additional, Beisker, Wolfgang, additional, Benes, Vladimir, additional, Beyaert, Rudi, additional, Blanco, Alfonso, additional, Boardman, Dominic A., additional, Bogdan, Christian, additional, Borger, Jessica G., additional, Borsellino, Giovanna, additional, Boulais, Philip E., additional, Bradford, Jolene A., additional, Brenner, Dirk, additional, Brinkman, Ryan R., additional, Brooks, Anna E. S., additional, Busch, Dirk H., additional, Büscher, Martin, additional, Bushnell, Timothy P., additional, Calzetti, Federica, additional, Cameron, Garth, additional, Cammarata, Ilenia, additional, Cao, Xuetao, additional, Cardell, Susanna L., additional, Casola, Stefano, additional, Cassatella, Marco A., additional, Cavani, Andrea, additional, Celada, Antonio, additional, Chatenoud, Lucienne, additional, Chattopadhyay, Pratip K., additional, Chow, Sue, additional, Christakou, Eleni, additional, Čičin‐Šain, Luka, additional, Clerici, Mario, additional, Colombo, Federico S., additional, Cook, Laura, additional, Cooke, Anne, additional, Cooper, Andrea M., additional, Corbett, Alexandra J., additional, Cosma, Antonio, additional, Cosmi, Lorenzo, additional, Coulie, Pierre G., additional, Cumano, Ana, additional, Cvetkovic, Ljiljana, additional, Dang, Van Duc, additional, Dang‐Heine, Chantip, additional, Davey, Martin S., additional, Davies, Derek, additional, De Biasi, Sara, additional, Del Zotto, Genny, additional, Dela Cruz, Gelo Victoriano, additional, Delacher, Michael, additional, Della Bella, Silvia, additional, Dellabona, Paolo, additional, Deniz, Günnur, additional, Dessing, Mark, additional, Di Santo, James P., additional, Diefenbach, Andreas, additional, Dieli, Francesco, additional, Dolf, Andreas, additional, Dörner, Thomas, additional, Dress, Regine J., additional, Dudziak, Diana, additional, Dustin, Michael, additional, Dutertre, Charles‐Antoine, additional, Ebner, Friederike, additional, Eckle, Sidonia B. G., additional, Edinger, Matthias, additional, Eede, Pascale, additional, Ehrhardt, Götz R.A., additional, Eich, Marcus, additional, Engel, Pablo, additional, Engelhardt, Britta, additional, Erdei, Anna, additional, Esser, Charlotte, additional, Everts, Bart, additional, Evrard, Maximilien, additional, Falk, Christine S., additional, Fehniger, Todd A., additional, Felipo‐Benavent, Mar, additional, Ferry, Helen, additional, Feuerer, Markus, additional, Filby, Andrew, additional, Filkor, Kata, additional, Fillatreau, Simon, additional, Follo, Marie, additional, Förster, Irmgard, additional, Foster, John, additional, Foulds, Gemma A., additional, Frehse, Britta, additional, Frenette, Paul S., additional, Frischbutter, Stefan, additional, Fritzsche, Wolfgang, additional, Galbraith, David W., additional, Gangaev, Anastasia, additional, Garbi, Natalio, additional, Gaudilliere, Brice, additional, Gazzinelli, Ricardo T., additional, Geginat, Jens, additional, Gerner, Wilhelm, additional, Gherardin, Nicholas A., additional, Ghoreschi, Kamran, additional, Gibellini, Lara, additional, Ginhoux, Florent, additional, Goda, Keisuke, additional, Godfrey, Dale I., additional, Goettlinger, Christoph, additional, González‐Navajas, Jose M., additional, Goodyear, Carl S., additional, Gori, Andrea, additional, Grogan, Jane L., additional, Grummitt, Daryl, additional, Grützkau, Andreas, additional, Haftmann, Claudia, additional, Hahn, Jonas, additional, Hammad, Hamida, additional, Hämmerling, Günter, additional, Hansmann, Leo, additional, Hansson, Goran, additional, Harpur, Christopher M., additional, Hartmann, Susanne, additional, Hauser, Andrea, additional, Hauser, Anja E., additional, Haviland, David L., additional, Hedley, David, additional, Hernández, Daniela C., additional, Herrera, Guadalupe, additional, Herrmann, Martin, additional, Hess, Christoph, additional, Höfer, Thomas, additional, Hoffmann, Petra, additional, Hogquist, Kristin, additional, Holland, Tristan, additional, Höllt, Thomas, additional, Holmdahl, Rikard, additional, Hombrink, Pleun, additional, Houston, Jessica P., additional, Hoyer, Bimba F., additional, Huang, Bo, additional, Huang, Fang‐Ping, additional, Huber, Johanna E., additional, Huehn, Jochen, additional, Hundemer, Michael, additional, Hunter, Christopher A., additional, Hwang, William Y. K., additional, Iannone, Anna, additional, Ingelfinger, Florian, additional, Ivison, Sabine M, additional, Jäck, Hans‐Martin, additional, Jani, Peter K., additional, Jávega, Beatriz, additional, Jonjic, Stipan, additional, Kaiser, Toralf, additional, Kalina, Tomas, additional, Kamradt, Thomas, additional, Kaufmann, Stefan H. E., additional, Keller, Baerbel, additional, Ketelaars, Steven L. C., additional, Khalilnezhad, Ahad, additional, Khan, Srijit, additional, Kisielow, Jan, additional, Klenerman, Paul, additional, Knopf, Jasmin, additional, Koay, Hui‐Fern, additional, Kobow, Katja, additional, Kolls, Jay K., additional, Kong, Wan Ting, additional, Kopf, Manfred, additional, Korn, Thomas, additional, Kriegsmann, Katharina, additional, Kristyanto, Hendy, additional, Kroneis, Thomas, additional, Krueger, Andreas, additional, Kühne, Jenny, additional, Kukat, Christian, additional, Kunkel, Désirée, additional, Kunze‐Schumacher, Heike, additional, Kurosaki, Tomohiro, additional, Kurts, Christian, additional, Kvistborg, Pia, additional, Kwok, Immanuel, additional, Landry, Jonathan, additional, Lantz, Olivier, additional, Lanuti, Paola, additional, LaRosa, Francesca, additional, Lehuen, Agnès, additional, LeibundGut‐Landmann, Salomé, additional, Leipold, Michael D., additional, Leung, Leslie Y.T., additional, Levings, Megan K., additional, Lino, Andreia C., additional, Liotta, Francesco, additional, Litwin, Virginia, additional, Liu, Yanling, additional, Ljunggren, Hans‐Gustaf, additional, Lohoff, Michael, additional, Lombardi, Giovanna, additional, Lopez, Lilly, additional, López‐Botet, Miguel, additional, Lovett‐Racke, Amy E., additional, Lubberts, Erik, additional, Luche, Herve, additional, Ludewig, Burkhard, additional, Lugli, Enrico, additional, Lunemann, Sebastian, additional, Maecker, Holden T., additional, Maggi, Laura, additional, Maguire, Orla, additional, Mair, Florian, additional, Mair, Kerstin H., additional, Mantovani, Alberto, additional, Manz, Rudolf A., additional, Marshall, Aaron J., additional, Martínez‐Romero, Alicia, additional, Martrus, Glòria, additional, Marventano, Ivana, additional, Maslinski, Wlodzimierz, additional, Matarese, Giuseppe, additional, Mattioli, Anna Vittoria, additional, Maueröder, Christian, additional, Mazzoni, Alessio, additional, McCluskey, James, additional, McGrath, Mairi, additional, McGuire, Helen M., additional, McInnes, Iain B., additional, Mei, Henrik E., additional, Melchers, Fritz, additional, Melzer, Susanne, additional, Mielenz, Dirk, additional, Miller, Stephen D., additional, Mills, Kingston H.G., additional, Minderman, Hans, additional, Mjösberg, Jenny, additional, Moore, Jonni, additional, Moran, Barry, additional, Moretta, Lorenzo, additional, Mosmann, Tim R., additional, Müller, Susann, additional, Multhoff, Gabriele, additional, Muñoz, Luis Enrique, additional, Münz, Christian, additional, Nakayama, Toshinori, additional, Nasi, Milena, additional, Neumann, Katrin, additional, Ng, Lai Guan, additional, Niedobitek, Antonia, additional, Nourshargh, Sussan, additional, Núñez, Gabriel, additional, O'Connor, José‐Enrique, additional, Ochel, Aaron, additional, Oja, Anna, additional, Ordonez, Diana, additional, Orfao, Alberto, additional, Orlowski‐Oliver, Eva, additional, Ouyang, Wenjun, additional, Oxenius, Annette, additional, Palankar, Raghavendra, additional, Panse, Isabel, additional, Pattanapanyasat, Kovit, additional, Paulsen, Malte, additional, Pavlinic, Dinko, additional, Penter, Livius, additional, Peterson, Pärt, additional, Peth, Christian, additional, Petriz, Jordi, additional, Piancone, Federica, additional, Pickl, Winfried F., additional, Piconese, Silvia, additional, Pinti, Marcello, additional, Pockley, A. Graham, additional, Podolska, Malgorzata Justyna, additional, Poon, Zhiyong, additional, Pracht, Katharina, additional, Prinz, Immo, additional, Pucillo, Carlo E. M., additional, Quataert, Sally A., additional, Quatrini, Linda, additional, Quinn, Kylie M., additional, Radbruch, Helena, additional, Radstake, Tim R. D. J., additional, Rahmig, Susann, additional, Rahn, Hans‐Peter, additional, Rajwa, Bartek, additional, Ravichandran, Gevitha, additional, Raz, Yotam, additional, Rebhahn, Jonathan A., additional, Recktenwald, Diether, additional, Reimer, Dorothea, additional, Reis e Sousa, Caetano, additional, Remmerswaal, Ester B.M., additional, Richter, Lisa, additional, Rico, Laura G., additional, Riddell, Andy, additional, Rieger, Aja M., additional, Robinson, J. Paul, additional, Romagnani, Chiara, additional, Rubartelli, Anna, additional, Ruland, Jürgen, additional, Saalmüller, Armin, additional, Saeys, Yvan, additional, Saito, Takashi, additional, Sakaguchi, Shimon, additional, Sala‐de‐Oyanguren, Francisco, additional, Samstag, Yvonne, additional, Sanderson, Sharon, additional, Sandrock, Inga, additional, Santoni, Angela, additional, Sanz, Ramon Bellmàs, additional, Saresella, Marina, additional, Sautes‐Fridman, Catherine, additional, Sawitzki, Birgit, additional, Schadt, Linda, additional, Scheffold, Alexander, additional, Scherer, Hans U., additional, Schiemann, Matthias, additional, Schildberg, Frank A., additional, Schimisky, Esther, additional, Schlitzer, Andreas, additional, Schlosser, Josephine, additional, Schmid, Stephan, additional, Schmitt, Steffen, additional, Schober, Kilian, additional, Schraivogel, Daniel, additional, Schuh, Wolfgang, additional, Schüler, Thomas, additional, Schulte, Reiner, additional, Schulz, Axel Ronald, additional, Schulz, Sebastian R., additional, Scottá, Cristiano, additional, Scott‐Algara, Daniel, additional, Sester, David P., additional, Shankey, T. Vincent, additional, Silva‐Santos, Bruno, additional, Simon, Anna Katharina, additional, Sitnik, Katarzyna M., additional, Sozzani, Silvano, additional, Speiser, Daniel E., additional, Spidlen, Josef, additional, Stahlberg, Anders, additional, Stall, Alan M., additional, Stanley, Natalie, additional, Stark, Regina, additional, Stehle, Christina, additional, Steinmetz, Tobit, additional, Stockinger, Hannes, additional, Takahama, Yousuke, additional, Takeda, Kiyoshi, additional, Tan, Leonard, additional, Tárnok, Attila, additional, Tiegs, Gisa, additional, Toldi, Gergely, additional, Tornack, Julia, additional, Traggiai, Elisabetta, additional, Trebak, Mohamed, additional, Tree, Timothy I.M., additional, Trotter, Joe, additional, Trowsdale, John, additional, Tsoumakidou, Maria, additional, Ulrich, Henning, additional, Urbanczyk, Sophia, additional, van de Veen, Willem, additional, van den Broek, Maries, additional, van der Pol, Edwin, additional, Van Gassen, Sofie, additional, Van Isterdael, Gert, additional, van Lier, René A.W., additional, Veldhoen, Marc, additional, Vento‐Asturias, Salvador, additional, Vieira, Paulo, additional, Voehringer, David, additional, Volk, Hans‐Dieter, additional, von Borstel, Anouk, additional, von Volkmann, Konrad, additional, Waisman, Ari, additional, Walker, Rachael V., additional, Wallace, Paul K., additional, Wang, Sa A., additional, Wang, Xin M., additional, Ward, Michael D., additional, Ward‐Hartstonge, Kirsten A, additional, Warnatz, Klaus, additional, Warnes, Gary, additional, Warth, Sarah, additional, Waskow, Claudia, additional, Watson, James V., additional, Watzl, Carsten, additional, Wegener, Leonie, additional, Weisenburger, Thomas, additional, Wiedemann, Annika, additional, Wienands, Jürgen, additional, Wilharm, Anneke, additional, Wilkinson, Robert John, additional, Willimsky, Gerald, additional, Wing, James B., additional, Winkelmann, Rieke, additional, Winkler, Thomas H., additional, Wirz, Oliver F., additional, Wong, Alicia, additional, Wurst, Peter, additional, Yang, Jennie H. M., additional, Yang, Juhao, additional, Yazdanbakhsh, Maria, additional, Yu, Liping, additional, Yue, Alice, additional, Zhang, Hanlin, additional, Zhao, Yi, additional, Ziegler, Susanne Maria, additional, Zielinski, Christina, additional, Zimmermann, Jakob, additional, and Zychlinsky, Arturo, additional

Published
2019
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