37 results on '"Tamar, Tak"'
Search Results
2. Metabolic heterogeneity of tissue-resident macrophages in homeostasis and during helminth infection
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Graham A. Heieis, Thiago A. Patente, Luís Almeida, Frank Vrieling, Tamar Tak, Georgia Perona-Wright, Rick M. Maizels, Rinke Stienstra, and Bart Everts
- Subjects
Science - Abstract
Abstract Tissue-resident macrophage populations constitute a mosaic of phenotypes, yet how their metabolic states link to the range of phenotypes and functions in vivo is still poorly defined. Here, using high-dimensional spectral flow cytometry, we observe distinct metabolic profiles between different organs and functionally link acetyl CoA carboxylase activity to efferocytotic capacity. Additionally, differences in metabolism are evident within populations from a specific site, corresponding to relative stages of macrophage maturity. Immune perturbation with intestinal helminth infection increases alternative activation and metabolic rewiring of monocyte-derived macrophage populations, while resident TIM4+ intestinal macrophages remain immunologically and metabolically hyporesponsive. Similar metabolic signatures in alternatively-activated macrophages are seen from different tissues using additional helminth models, but to different magnitudes, indicating further tissue-specific contributions to metabolic states. Thus, our high-dimensional, flow-based metabolic analyses indicates complex metabolic heterogeneity and dynamics of tissue-resident macrophage populations at homeostasis and during helminth infection.
- Published
- 2023
- Full Text
- View/download PDF
3. CellDestiny: A RShiny application for the visualization and analysis of single-cell lineage tracing data
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Louisa Hadj Abed, Tamar Tak, Jason Cosgrove, and Leïla Perié
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lineage tracing ,single-cell ,bioinformatics ,gene therapy ,data analysis ,lentiviral barcoding ,Medicine (General) ,R5-920 - Abstract
Single-cell lineage tracing permits the labeling of individual cells with a heritable marker to follow the fate of each cell’s progeny. Over the last twenty years, several single-cell lineage tracing methods have emerged, enabling major discoveries in developmental biology, oncology and gene therapies. Analytical tools are needed to draw meaningful conclusions from lineage tracing measurements, which are characterized by high variability, sparsity and technical noise. However, the single cell lineage tracing field lacks versatile and easy-to-use tools for standardized and reproducible analyses, in particular tools accessible to biologists. Here we present CellDestiny, a RShiny app and associated web application developed for experimentalists without coding skills to perform visualization and analysis of single cell lineage-tracing datasets through a graphical user interface. We demonstrate the functionality of CellDestiny through the analysis of (i) lentiviral barcoding datasets of murine hematopoietic progenitors; (ii) published integration site data from Wiskott-Aldrich Symdrome patients undergoing gene-therapy treatment; and (iii) simultaneous barcoding and transcriptomic analysis of murine hematopoietic progenitor differentiation in vitro. In summary, CellDestiny is an easy-to-use and versatile toolkit that enables biologists to visualize and analyze single-cell lineage tracing data.
- Published
- 2022
- Full Text
- View/download PDF
4. Erythropoietin directly remodels the clonal composition of murine hematopoietic multipotent progenitor cells
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Almut S Eisele, Jason Cosgrove, Aurelie Magniez, Emilie Tubeuf, Sabrina Tenreira Bento, Cecile Conrad, Fanny Cayrac, Tamar Tak, Anne-Marie Lyne, Jos Urbanus, and Leïla Perié
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cellular barcoding ,erythropoietin ,hematopoietic stem cell ,multipotent progenitor ,single cell ,Medicine ,Science ,Biology (General) ,QH301-705.5 - Abstract
The cytokine erythropoietin (EPO) is a potent inducer of erythrocyte development and one of the most prescribed biopharmaceuticals. The action of EPO on erythroid progenitor cells is well established, but its direct action on hematopoietic stem and progenitor cells (HSPCs) is still debated. Here, using cellular barcoding, we traced the differentiation of hundreds of single murine HSPCs, after ex vivo EPO exposure and transplantation, in five different hematopoietic cell lineages, and observed the transient occurrence of high-output myeloid-erythroid-megakaryocyte-biased and myeloid-B-cell-dendritic cell-biased clones. Single-cell RNA sequencing analysis of ex vivo EPO-exposed HSPCs revealed that EPO induced the upregulation of erythroid associated genes in a subset of HSPCs, overlapping with multipotent progenitor (MPP) 1 and MPP2. Transplantation of barcoded EPO-exposed MPP2 confirmed their enrichment in myeloid-erythroid-biased clones. Collectively, our data show that EPO does act directly on MPP independent of the niche and modulates fate by remodeling the clonal composition of the MPP pool.
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- 2022
- Full Text
- View/download PDF
5. Differential effects of short- and long-term treatment with mepolizumab on eosinophil kinetics in blood and sputum in eosinophilic asthma
- Author
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Marwan Hassani, Tamar Tak, Corneli van Aalst, Saar van Nederveen, Kiki Tesselaar, Nienke Vrisekoop, and Leo Koenderman
- Subjects
Health sciences ,Immunology ,Respiratory medicine ,Clinical medicine ,Drugs ,Science - Abstract
Summary: Mepolizumab (anti-IL-5) is a successful biological for treatment of T2/eosinophilic asthma by blocking the IL-5-eosinophil axis. The kinetics of human eosinophils in blood and sputum was determined to better understand the underlying mechanism(s). Pulse-chase labeling was performed with 6,6-2H2-glucose in patients with asthma after short term (4 days) and long term (84 days) treatment with mepolizumab (n = 10) or placebo (n = 10). The retention time of eosinophils in sputum was longer than in blood. Treatment with mepolizumab induced a fast and long-lasting eosinopenia with no reduction of eosinophil progenitors. The retention time of eosinophils in blood was delayed only after short-term treatment. This leads to the hypothesis that IL-5 increases the number of IL-5-responsive progenitors and potentiates homing to the tissues, leading to reactive eosinophilia. Long-term treatment is associated with low numbers of IL-5-independent eosinophils in blood and tissues. Therefore, long-term treatment with mepolizumab restores the kinetics of eosinophils as normally found in homeostasis.
- Published
- 2021
- Full Text
- View/download PDF
6. HSPCs display within-family homogeneity in differentiation and proliferation despite population heterogeneity
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Tamar Tak, Giulio Prevedello, Gaël Simon, Noémie Paillon, Camélia Benlabiod, Caroline Marty, Isabelle Plo, Ken R Duffy, and Leïla Perié
- Subjects
haematopoietic stem ,progenitor cell ,concordance ,cell differentiation ,cell proliferation ,Medicine ,Science ,Biology (General) ,QH301-705.5 - Abstract
High-throughput single-cell methods have uncovered substantial heterogeneity in the pool of hematopoietic stem and progenitor cells (HSPCs), but how much instruction is inherited by offspring from their heterogeneous ancestors remains unanswered. Using a method that enables simultaneous determination of common ancestor, division number, and differentiation status of a large collection of single cells, our data revealed that murine cells that derived from a common ancestor had significant similarities in their division progression and differentiation outcomes. Although each family diversifies, the overall collection of cell types observed is composed of homogeneous families. Heterogeneity between families could be explained, in part, by differences in ancestral expression of cell surface markers. Our analyses demonstrate that fate decisions of cells are largely inherited from ancestor cells, indicating the importance of common ancestor effects. These results may have ramifications for bone marrow transplantation and leukemia, where substantial heterogeneity in HSPC behavior is observed.
- Published
- 2021
- Full Text
- View/download PDF
7. Differential antibacterial control by neutrophil subsets
- Author
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Pieter H.C. Leliefeld, Janesh Pillay, Nienke Vrisekoop, Marjolein Heeres, Tamar Tak, Matthijs Kox, Suzan H.M. Rooijakkers, Taco W. Kuijpers, Peter Pickkers, Luke P.H. Leenen, and Leo Koenderman
- Subjects
Specialties of internal medicine ,RC581-951 - Abstract
Abstract: Neutrophils comprise a heterogeneous population of cells essential for bacterial eradication, and defects in neutrophil function are associated with increased susceptibility to infection. In this study, neutrophils from healthy controls were shown to prevent bacterial proliferation for at least 48 hours when cocultured with methicillin-resistant Staphylococcus aureus (MRSA) in tissue-like scaffolds by establishing a bacteriostatic environment inside their phagolysosome. This intracellular bacterial containment is independent of reactive oxygen species because neutrophils that lack a functional nicotinamide adenine dinucleotide phosphate–oxidase complex displayed no defect in intracellular bacterial containment, whereas killing of the pathogen was impaired. During acute inflammation, a subset of CD16bright/CD62Ldim hypersegmented neutrophils displayed normal phagocytosis associated with a remarkably poor capacity to contain bacteria intracellularly. Conversely, CD16dim-banded neutrophils were the only neutrophil subset that adequately contained MRSA. These findings demonstrate a clear neutrophil heterogeneity in their antimicrobial capacity and the appearance of neutrophil subsets with a clear differentiation in functionality during acute inflammation. Furthermore, this study provides an evolutionary basis for the rapid release of banded neutrophils into the circulation during acute inflammation.
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- 2018
- Full Text
- View/download PDF
8. Proceedings of the 23rd Paediatric Rheumatology European Society Congress: part three
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Riccardo Papa, Alessandro Consolaro, Francesca Minoia, Roberta Caorsi, Gianmichele Magnano, Marco Gattorno, Angelo Ravelli, Paolo Picco, Roberto Pillon, Denise Pires Marafon, Lidia Meli, Claudia Bracaglia, Andrea Taddio, Fabrizio De Benedetti, Enes Turan, Sara Sebnem Kilic, Yasuhiko Itoh, Tomoko Shigemori, Shingo Yamanishi, Hidehiko Nagasaki, Ela Tarakci, Nilay Arman, Devrim Tarakci, Yusuf S. Akgul, Ozgur Kasapcopur, Emily Wilson, Hanna Lythgoe, Eve Smith, Jenny Preston, Michael W. Beresford, Lynn R. Spiegel, Jennifer Stinson, Mark Connelly, Adam Huber, Nadia Luca, Argerie Tsimicalis, Stephanie Luca, Naweed Tajuddin, Roberta Berard, Julie Barsalou, Sarah Campillo, Brian Feldman, Shirley Tse, Paul Dancey, Ciaran Duffy, Nicole Johnson, Patrick McGrath, Natalie Shiff, Lori Tucker, Charles Victor, Chitra Lalloo, Lauren Harris, Joseph Cafazzo, Kristin Houghton, Ronald Laxer, Madeleine Rooney, Roisin Campbell, Catherine Wright, Wineke Armbrust, Otto Lelieveld, Jolanda Tuinstra, Nico Wulffraat, Joyce Bos, Jeanette Cappon, Marion van Rossum, Mariët Hagedoorn, Anna Vermé, Ylva Lampela, Ayse Huri Ozdogan, S. Ugurlu, K. Barut, A. Androvic, O. Kasapçopu, Jody Etheridge, Katie Dobson, Sue Kemp, AnnaCarin Horne, Karin Palmblad, Malin Höglund, Natalia Stepanenko, Svetlana Salugina, Evgeny Fedorov, Irina Nikishina, Maria Kaleda, Kenan Barut, Amra Adrovic, Sezgin Sahin, Laurence Toumoulin, Johnny Frossard, Stephanie Archimbaut, Anne Paitier, Rolande Guastalli, Severine Guillaume Czitrom, Sirirat Charuvanij, Chollada Chaiyadech, Takako Miyamae, Hisashi Yamanaka, Cecile Picard, Guillaume Thouvenin, Caroline Kannengiesser, Jean-Christophe Dubus, Nadia Jeremiah, Frédéric Rieux-Laucat, Bruno Crestani, Véronique Secq, Christelle Ménard, Martine Reynaud-Gaubert, Françoise Thivolet-Bejui, Philippe Reix, Alexandre Belot, Ezgi Deniz Batu, Hafize Emine Sonmez, Abdulsamet Erden, Ekim Z. Taskiran, Omer Karadag, Umut Kalyoncu, İbrahim Oncel, Berkan Kaplan, Zehra Serap Arici, Cagri Mesut Temucin, Haluk Topaloglu, Yelda Bilginer, Mehmet Alikasifoglu, Seza Ozen, Lien Van Eyck, Ellen De Langhe, Isabelle Jéru, Erika Van Nieuwenhove, Vasiliki Lagou, Paul J. Baker, Jocelyn Garcia-Perez, James Dooley, Lien De Somer, Raf Sciot, Pierre-Yves Jeandel, Julia Ruuth-Praz, Bruno Copin, Myrna Medley-Hashim, Andre Megarbane, Sinisa Savic, An Goris, Serge Amselem, Adrian Liston, Seth Masters, Carine Wouters, Nami Okamoto, Yuko Sugita, Kousuke Shabana, Takuji Murata, Hiroshi Tamai, Juliana Ferenczová, Erika Banóova, Pavol Mrážik, Veronika Vargova, Dubravko Bajramovic, Ksenija Stekic Novacki, Kristina Potocki, Marijan Frkovic, Marija Jelusic, Olga Kostareva, Svetlana Arsenyeva, Anna Shapovalenko, Lennart Jans, Nele Herregods, Jacob Jaremko, Rik Joos, Joke Dehoorne, Xenofon Baraliakos, Sofia Ramiro, Julio C. Casasola-Vargas, Désirée van der Heijde, Robert Landewé, Ruben Burgos-Vargas, Shirley M. Tse, Gerd Horneff, Kristina Unnebrink, Jaclyn K. Anderson, Aysenur Paç Kisaarslan, Betül Sözeri, Zübeyde Gündüz, Gökmen Zararsız, Hakan Poyrazoğlu, Ruhan Düşünsel, Kazutaka Ouchi, Shinji Akioka, Hiroshi Kubo, Norio Nakagawa, Hajime Hosoi, Lovro Lamot, Fran Borovecki, Sanja Kapitanovic, Kristina Gotovac, Mandica Vidovic, Mirta Lamot, Edi Paleka Bosak, Miroslav Harjacek, Ricardo A. Russo, María M. Katsicas, Ruben Burgos Vargas, Ana L. Ortiz-Peyegahud, Zhang Pingping, Mou Yikun, Qi Jun, Jiang Yutong, Gu Jieruo, Mikhail M. Kostik, Shilova Ekaterina, Ilia Avrusin, Yuriy Korin, Olga Kopchak, Eugenia Isupova, Irina Chikova, Panova Tatyana, Margarita Dubko, Vera Masalova, Ludmila Snegireva, Tatyana Kornishina, Olga Kalashnikova, Vyacheslav Chasnyk, Tatyana Likhacheva, N. Ruperto, H. I. Brunner, P. Quartier, T. Constantin, E. Alexeeva, R. Schneider, I. Kone-Paut, K. Schikler, K. Marzan, N. Wulffraat, S. Padeh, V. Chasnyk, C. Wouters, J. B. Kuemmerle-Deschner, T. Kallinich, B. Lauwerys, E. Haddad, E. Nasonov, M. Trachana, O. Vougiouka, K. Leon, A. Speziale, K. Lheritier, E. Vritzali, A. Martini, D. Lovell, PRINTO/PRCSG, Nienke Ter Haar, Rianne Scholman, Wilco de Jager, Tamar Tak, Pieter Leliefeld, Bas Vastert, Sytze de Roock, Ariane de Ganck, Nadia Ryter, Miha Lavric, Dirk Foell, Renee F. Modica, Kathleen G. Lomax, Pamela Batzel, Armelle Cassanas, Melissa E. Elder, Rina Denisova, Ekaterina Alexeeva, Saniya Valieva, Tatyana Bzarova, Kseniya Isayeva, Tatyana Sleptsova, Olga Lomakina, Alexandra Chomahidze, Margarita Soloshenko, Meyry Shingarova, Elena Kachshenko, Wilco De Jager, Sebastiaan J. Vastert, Gerdien Mijnheer, Berent J. Prakken, Nico M. Wulffraat, Hafize E. Sönmez, Asuman N. Karhan, Ezgi D. Batu, Zehra S. Arıcı, Ersin Gümüş, Hülya Demir, Aysel Yüce, Seza Özen, Jasmina Ahluwalia, Bhavneet Bharti, Sweta Rajpal, Varun Uppal, Alaknanda Walia, Surjit S. Samlok, Narender Kumar, Clarissa C. Valões, Beatriz C. Molinari, Ana Claudia G. Pitta, Natali W. Gormezano, Sylvia C. Farhat, Kátia Kozu, Adriana M. Sallum, Simone Appenzeller, Ana Paula Sakamoto, Maria T. Terreri, Rosa M. Pereira, Claudia S. Magalhães, Cássia Maria Barbosa, Francisco Hugo Gomes, Eloisa Bonfá, Clovis A. Silva, Kubra Ozturk, Zelal Ekinci, Maie Helal, Natalia Cabrera, Jean Christophe Lega, Jocelyne Drai, Rene Ecochard, O. V. Shpitonkova, N. S. Podchernyaeva, Y. O. Kostina, N. G. Dashkova, M. K. Osminina, Gozde Yucel, Ahmet Arvas, Nandini Moorthy, Paraskevi Dimou, Angela Midgley, Matthew Peak, Simon C. Satchell, Rachael D. Wright, Rachel Corkhill, Eve M. Smith, Sagar Bhattad, Amit Rawat, Surjit Singh, Anju Gupta, Deepti Suri, Martin de Boer, Taco Kuijpers, Vignesh Pandiarajan, Sapna Sandal, Sebastian Giraldo, Roy Sanguino, Adriana S. Diaz, Selcuk Uzuner, Gizem Durcan, Ali Guven Kilicoglu, Ayhan Bilgic, Kayhan Bahali, Sinem Durmus, Hafize Uzun, Nur Canpolat, Salim Caliskan, Lale Sever, Tomomi Sato, Fuminori Kimura, Wafaa Suwairi, Reem Abdwani, Abdulaziz Al Rowais, Jubran Al qanatish, Abdulrahman Al Asiri, Ekaterina Gaidar, Mikhail Kostik, Elena Serogodskaya, Tatyana Nikitina, Evgenia Isupova, Elham Sardar, Perrine Dusser, Antoine Rousseau, Marc Labetoulle, Emanuel Barreau, Bahram Bodaghi, Isabelle Kone-Paut, Ivan Foeldvari, Jordi Anton, Rosa Bou, Sheila Angeles-Han, Regitze Bangsgaard, Gabriele Brumm, Tamas Constantin, Clive Edelsten, Jens Klotsche, Kirsten Minden, Elisabetta Miserocchi, Susan Nielsen, Gabriele Simonini, Arnd Heiligenhaus, Juan Manuel Mosquera Angarita, Carmen Garcia de Vicuña, Maria Victoria Hernandez, Alfredo Adan, Victor Llorens, Rosa Alcobendas, Susana Noval, Juan Carlos Lopez Robledillo, Isabel Valls, Mari Carmen Pinedo, Alejandro Fonollosa, Jaime de Inocencio, Pilar Tejada, Beatriz Bravo, Manuel Torribio, María Jesús García de Yebenes, Jordi Antón, Uveitis Working Group of the Spanish Pediatric Rheumatology Society, Lorenza Maria Argolini, Irene Pontikaki, Maria Orietta Borghi, Laura Cesana, Barbara Castiglioni, Maurizio Gattinara, Pierluigi Meroni, Pierre Quartier, Veronique Despert, Sylvaine Poignant, Amandine Baptiste, Caroline Elie, Laurent Kodjikian, Dominique Monnet, Michel Weber, Laura Moal, LuuLy Pham, Emmanuel Barreau, Cherif Titah, Pascal Dureau, Vanessa Cecchin, Maria Elisabetta Zannin, Daniele Ferrari, Francesco Comacchio, Rolando Cimaz, Fernanda Falcini, Antonella Petaccia, Stefania Viola, Luciana Breda, Francesco La Torre, Fabio Vittadello, Giorgia Martini, Francesco Zulian, Caroline Galeotti, Guillaume Sarrabay, Olivier Fogel, Isabelle Touitou, Corinne Miceli-Richard, Isabelle Koné-Paut, Hala Etayari, Hashad Soad, Ihab El Kadry, Habibullah Eatamadi, Kais AlAlgawi, Mustafa Al Maini, Khulood Khawaja, Sophie Van den Berghe, Ilse de Schryver, Ann Raes, Lídia L. C. Teixeira, Ana Duarte, Sandra Sousa, Filipe Vinagre, Maria J. Santos, Nataly S. Shevchenko, Ludmila F. Bogmat, Marina V. Demyanenko, Navdha R. Ramchurn, Mark Friswell, Rebecca A. James, Lucy R. Wedderburn, Reshma Pattani, Clarissa A. Pilkington, Sandrine Compeyrot-Lacassagne, Ana V. Villarreal, Nydia Acevedo, Enrique Faugier, Rocio Maldonado, Dilek Yılmaz, Hilal Bektaş Uysal, Elena Kamenets, Ekaterina Zaharova, Stefka Radenska-Lopovok, Joao Nascimento, Helena Sofia, Carla Zilhão, Rui Almeida, Margarida Guedes, Murat Deveci, Svetlana Rodionovskaya, Vera Vinnikova, Irina Tsymbal, Edyta Olesińska, Jacek Postępski, Agnieszka Mroczkowska-Juchkiewicz, Agnieszka Pawłowska-Kamieniak, Beata Chrapko, Damjana Ključevšek, Nina Emeršič, Nataša Toplak, Tadej Avčin, Faina Rokhlina, Galina Glazyrina, Natalia Kolyadina, Kwangnam Kim, Sinae Eom, Daeyoung Kim, Jungwoo Rhim, Francesca Ricci, Paola Montesano, Barbara Bonafini, Veronica Medeghini, Ilaria Parissenti, Antonella Meini, Marco Cattalini, Paolo Airò, Nataliya Panko, Nataliya Shevchenko, Iryna Lebec, Yevgeniya Zajceva, Sara Rostlund, Marie André, Takuma Hara, Takayuki Kishi, Yumi Tani, Aki Hanaya, Satoru Nagata, Velma Selmanovic, Aida Omercahic-Dizdarevic, Adisa Cengic, Almira Cosickic, Aida Omerčahić Dizdarević, Gemma Lepri, Clara Malattia, Eleonora Bellucci, Marco Matucci-Cerinic, Anton Solovyev, Elena Fedotova, Ana Victoria Villarreal, Talia Diaz, Yuridiana Ramirez, Teresa Giani, Achille Marino, Daniel Hunt, Muthana Al Obaidi, Veli Veli, Charalampia Papadopoulou, Jochen Kammermeier, Anna Poluha, Gangadhara C. Bharmappanavara, Alison Kelly, Lindsay Shaw, Giovanna Ferrara, Michele Luzzati, Mattia Giovannini, Liliana Jurado, Juliana Chamorro, Lorena Sarmiento, Ester Conversano, Maria Francesca Gicchino, Giulia Macchini, Carmela Granato, Assunta Tirelli, Alma N. Olivieri, Marija Perica, Lana Tambić Bukovac, Reza Sinaei, Vadood Javadi Parvaneh, Reza Shiari, Khosro Rahmani, Fatemeh F. Mehregan, Mehrnoush Hassas Yeganeh, Inmaculada Calvo Penadés, Berta López Montesinos, Ma Isabel González Fernández, Adriana Rodríguez Vidal, Anand Prahalad Rao, Ayesha Romana, Jyothi Raghuram, Ankur Kumar, Vishali Gupta, Elif Comak, Gülşah Kaya Aksoy, Aygen Yılmaz, Atike Atalay, Mustafa Koyun, Reha Artan, Sema Akman, Maria I. Kaleda, Irina P. Nikishina, Sergei K. Soloviev, Victor A. Malievsky, Ekaterina V. Nikolaeva, Agnieszka Gazda, Beata Kołodziejczyk, Lidia Rutkowska-Sak, Angela Mauro, Pierluigi Marzuillo, Stefano Guarino, and Angela La Manna
- Subjects
Pediatrics ,RJ1-570 ,Diseases of the musculoskeletal system ,RC925-935 - Published
- 2017
- Full Text
- View/download PDF
9. Simultaneous Assessment of Kinship, Division Number, and Phenotype via Flow Cytometry for Hematopoietic Stem and Progenitor Cells
- Author
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Alessandro Donada, Tamar Tak, Giulio Prevedello, Idan Milo, Ken R. Duffy, and Leïla Perié
- Subjects
General Immunology and Microbiology ,General Chemical Engineering ,General Neuroscience ,General Biochemistry, Genetics and Molecular Biology - Published
- 2023
10. The journey of neutropoiesis: how complex landscapes in bone marrow guide continuous neutrophil lineage determination
- Author
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Celine Overbeeke, Tamar Tak, and Leo Koenderman
- Subjects
Bone Marrow ,Neutrophils ,Immunology ,Homeostasis ,Cell Differentiation ,Cell Biology ,Hematology ,Hematopoietic Stem Cells ,Biochemistry - Abstract
Neutrophils are the most abundant white blood cell, and they differentiate in homeostasis in the bone marrow from hematopoietic stem cells (HSCs) via multiple intermediate progenitor cells into mature cells that enter the circulation. Recent findings support a continuous model of differentiation in the bone marrow of heterogeneous HSCs and progenitor populations. Cell fate decisions at the levels of proliferation and differentiation are enforced through expression of lineage-determining transcription factors and their interactions, which are influenced by intrinsic (intracellular) and extrinsic (extracellular) mechanisms. Neutrophil homeostasis is subjected to positive-feedback loops, stemming from the gut microbiome, as well as negative-feedback loops resulting from the clearance of apoptotic neutrophils by mature macrophages. Finally, the cellular kinetics regarding the replenishing of the mature neutrophil pool is discussed in light of recent contradictory data.
- Published
- 2022
11. Spectral flow cytometry reveals metabolic heterogeneity in tissue macrophages
- Author
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Graham A Heieis, Thiago A Patente, Tamar Tak, Luís Almeida, and Bart Everts
- Abstract
SummaryTissue-macrophage populations are constituted by a mosaic of phenotypes, yet new methods are needed to link metabolic status to the range of phenotypes in vivo. We therefore designed a high-dimensional panel for spectral flow cytometry to investigate the heterogeneity of tissue macrophage metabolism at steady-state, and their metabolic adaptation in response to infection. Distinct metabolic profiles were observed between tissue macrophages from different peripheral organs, as well as within populations from a specific site. As such, our data show multiple metabolic states in macrophages corresponding to relative stages of maturity in both the peritoneal cavity and small intestine. Immune perturbation with helminth infection further showed that peritoneal macrophages acquire an overall highly metabolically active profile, whereas responding intestinal macrophages displayed minimal changes in their metabolic phenotype. Thus, we demonstrate that high-dimensional, flow-based analysis is an exciting method to interrogate the metabolic heterogeneity and dynamics of tissue-macrophage populations.
- Published
- 2022
12. Author response: Erythropoietin directly remodels the clonal composition of murine hematopoietic multipotent progenitor cells
- Author
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Almut S Eisele, Jason Cosgrove, Aurelie Magniez, Emilie Tubeuf, Sabrina Tenreira Bento, Cecile Conrad, Fanny Cayrac, Tamar Tak, Anne-Marie Lyne, Jos Urbanus, and Leïla Perié
- Published
- 2022
13. In Vivo Tracking of Hematopoietic Stem and Progenitor Cell Ontogeny by Cellular Barcoding
- Author
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Tamar, Tak, Almut S, Eisele, and Leïla, Perié
- Subjects
Genetic Vectors ,Lentivirus ,Hematopoietic Stem Cell Transplantation ,High-Throughput Nucleotide Sequencing ,Mice, Transgenic ,Cell Separation ,Hematopoietic Stem Cells ,Polymerase Chain Reaction ,Hematopoiesis ,Mice ,HEK293 Cells ,Phenotype ,Cell Tracking ,Transduction, Genetic ,Animals ,Humans ,Cell Lineage ,Cell Proliferation - Abstract
Cellular barcoding is a powerful technique that allows for high-throughput mapping of the fate of single cells, notably hematopoietic stem and progenitor cells (HSPCs) after transplantation. Unique artificial DNA fragments, termed barcodes, are stably inserted into HSPCs using lentiviral transduction, making sure that each individual cell receives a single unique barcode. Barcoded HSPCs are transplanted into sublethally irradiated mice where they reconstitute the hematopoietic system through proliferation and differentiation. During this process, the barcode of each HSPC is inherited by all of its daughter cells and their subsequent mature hematopoietic cell progeny. After sorting mature hematopoietic cell subsets, their barcodes can be retrieved from genomic DNA through nested PCR and sequencing. Analysis of barcode sequencing results allows for determination of clonal relationships between the mature cells, that is, which cell types were produced by a single barcoded HSPC, as well as the heterogeneity of the initial HSPC population. Here, we give a detailed protocol of a complete HSPC cellular barcoding experiment, starting with barcode lentivirus production, isolation, transduction, and transplantation of HSPCs, isolation of target cells followed by PCR amplification and sequencing of DNA barcodes. Finally, we describe the basic filtering and analysis steps of barcode sequencing data to ensure high-quality results.
- Published
- 2021
14. HSPCs display within-family homogeneity in differentiation and proliferation despite population heterogeneity
- Author
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Ken R. Duffy, Tamar Tak, Leïla Perié, Caroline Marty, Gaël Simon, Camélia Benlabiod, Isabelle Plo, Giulio Prevedello, Noémie Paillon, Institut Curie [Paris], Laboratoire Physico-Chimie Curie [Institut Curie] (PCC), Institut Curie [Paris]-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre de Formation et de Recherche sur les Environnements Méditérranéens (CEFREM), Université de Perpignan Via Domitia (UPVD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut Gustave Roussy (IGR), Dynamique moléculaire de la transformation hématopoïétique (Dynamo), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Hamilton Institute [NUI], National University of Ireland [Galway] (NUI Galway), and Université de Perpignan Via Domitia (UPVD)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
0301 basic medicine ,concordance ,Cell type ,Mouse ,QH301-705.5 ,progenitor cell ,Cellular differentiation ,Science ,[SDV]Life Sciences [q-bio] ,Bone Marrow Cells ,Biology ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Bone Marrow ,medicine ,Animals ,Progenitor cell ,Biology (General) ,Cells, Cultured ,Ancestor ,[PHYS]Physics [physics] ,General Immunology and Microbiology ,Cluster of differentiation ,General Neuroscience ,Cell Differentiation ,General Medicine ,medicine.disease ,Hematopoietic Stem Cells ,Stem Cells and Regenerative Medicine ,Mice, Inbred C57BL ,Haematopoiesis ,Leukemia ,030104 developmental biology ,cell proliferation ,Evolutionary biology ,Medicine ,haematopoietic stem ,Stem cell ,030217 neurology & neurosurgery ,Research Article - Abstract
International audience; High-throughput single-cell methods have uncovered substantial heterogeneity in the pool of hematopoietic stem and progenitor cells (HSPCs), but how much instruction is inherited by offspring from their heterogeneous ancestors remains unanswered. Using a method that enables simultaneous determination of common ancestor, division number, and differentiation status of a large collection of single cells, our data revealed that murine cells that derived from a common ancestor had significant similarities in their division progression and differentiation outcomes. Although each family diversifies, the overall collection of cell types observed is composed of homogeneous families. Heterogeneity between families could be explained, in part, by differences in ancestral expression of cell surface markers. Our analyses demonstrate that fate decisions of cells are largely inherited from ancestor cells, indicating the importance of common ancestor effects. These results may have ramifications for bone marrow transplantation and leukemia, where substantial heterogeneity in HSPC behavior is observed.
- Published
- 2021
15. Author response: HSPCs display within-family homogeneity in differentiation and proliferation despite population heterogeneity
- Author
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Noémie Paillon, Tamar Tak, Giulio Prevedello, Gaël Simon, Caroline Marty, Ken R. Duffy, Camélia Benlabiod, Isabelle Plo, and Leïla Perié
- Subjects
Evolutionary biology ,Homogeneity (statistics) ,Population Heterogeneity ,Biology - Published
- 2021
16. Prolonged activation of nasal immune cell populations and development of tissue-resident SARS-CoV-2 specific CD8 T cell responses following COVID-19
- Author
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Shohreh Azimi, Dalebout T, Simon P. Jochems, Marion H. König, Pieter S. Hiemstra, Pothast Cr, Does Am, Jacqueline J. Janse, Verheij M, Zhang Jl, Meta Roestenberg, Anna H. Roukens, Maria Yazdanbakhsh, Corine Prins, Hermelijn H. Smits, Heemskerk Mh, Vries Jj, Hagedoorn Rs, Sesmu M. Arbous, Yvonne C. M. Kruize, Tamar Tak, Kikkert M, and Myeni Sk
- Subjects
medicine.anatomical_structure ,Immune system ,business.industry ,Immunology ,Cytotoxic T cell ,Medicine ,CD11c ,Mucous membrane of nose ,CD38 ,business ,Interleukin-7 receptor ,CD8 ,Respiratory tract - Abstract
The immune system plays a major role in Coronavirus Disease 2019 (COVID-19) pathogenesis, viral clearance and protection against re-infection. Immune cell dynamics during COVID-19 have been extensively documented in peripheral blood, but remain elusive in the respiratory tract. We performed minimally-invasive nasal curettage and mass cytometry to characterize nasal immune cells of COVID-19 patients during and 5-6 weeks after hospitalization. Contrary to observations in blood, no general T cell depletion at the nasal mucosa could be detected. Instead, we observed increased numbers of nasal granulocytes, monocytes, CD11c+ NK cells and exhausted CD4+ T effector memory cells during acute COVID-19 compared to age-matched healthy controls. These pro-inflammatory responses were found associated with viral load, while neutrophils also negatively correlated with oxygen saturation levels. Cell numbers mostly normalized following convalescence, except for persisting CD127+ granulocytes and activated T cells, including CD38+ CD8+ tissue-resident memory T cells. Moreover, we identified SARS-CoV-2 specific CD8+ T cells in the nasal mucosa in convalescent patients. Thus, COVID-19 has both transient and long-term effects on the immune system in the upper airway.
- Published
- 2021
17. Prolonged activation of nasal immune cell populations and development of tissue-resident SARS-CoV-2-specific CD8
- Author
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Anna H E, Roukens, Cilia R, Pothast, Marion, König, Wesley, Huisman, Tim, Dalebout, Tamar, Tak, Shohreh, Azimi, Yvonne, Kruize, Renate S, Hagedoorn, Mihaela, Zlei, Frank J T, Staal, Fenna J, de Bie, Jacques J M, van Dongen, Sesmu M, Arbous, Jaimie L H, Zhang, Maaike, Verheij, Corine, Prins, Anne M, van der Does, Pieter S, Hiemstra, Jutte J C, de Vries, Jacqueline J, Janse, Meta, Roestenberg, Sebenzile K, Myeni, Marjolein, Kikkert, Maria, Yazdanbakhsh, Mirjam H M, Heemskerk, Hermelijn H, Smits, Simon P, Jochems, and Frits, Rosendaal
- Subjects
CD4-Positive T-Lymphocytes ,Neutrophils ,SARS-CoV-2 ,COVID-19 ,HLA-DR Antigens ,Respiratory Mucosa ,CD8-Positive T-Lymphocytes ,Nose ,Antibodies, Viral ,Monocytes ,Killer Cells, Natural ,Memory T Cells ,Nasopharynx ,Humans ,Prospective Studies ,Granulocytes - Abstract
Systemic immune cell dynamics during coronavirus disease 2019 (COVID-19) are extensively documented, but these are less well studied in the (upper) respiratory tract, where severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replicates
- Published
- 2021
18. In Vivo Tracking of Hematopoietic Stem and Progenitor Cell Ontogeny by Cellular Barcoding
- Author
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Almut S Eisele, Leïla Perié, and Tamar Tak
- Subjects
0301 basic medicine ,education.field_of_study ,Cell division ,Population ,Biology ,Barcode ,Cell biology ,law.invention ,Transplantation ,03 medical and health sciences ,Transduction (genetics) ,Haematopoiesis ,genomic DNA ,030104 developmental biology ,0302 clinical medicine ,law ,Progenitor cell ,education ,030217 neurology & neurosurgery - Abstract
Cellular barcoding is a powerful technique that allows for high-throughput mapping of the fate of single cells, notably hematopoietic stem and progenitor cells (HSPCs) after transplantation. Unique artificial DNA fragments, termed barcodes, are stably inserted into HSPCs using lentiviral transduction, making sure that each individual cell receives a single unique barcode. Barcoded HSPCs are transplanted into sublethally irradiated mice where they reconstitute the hematopoietic system through proliferation and differentiation. During this process, the barcode of each HSPC is inherited by all of its daughter cells and their subsequent mature hematopoietic cell progeny. After sorting mature hematopoietic cell subsets, their barcodes can be retrieved from genomic DNA through nested PCR and sequencing. Analysis of barcode sequencing results allows for determination of clonal relationships between the mature cells, that is, which cell types were produced by a single barcoded HSPC, as well as the heterogeneity of the initial HSPC population. Here, we give a detailed protocol of a complete HSPC cellular barcoding experiment, starting with barcode lentivirus production, isolation, transduction, and transplantation of HSPCs, isolation of target cells followed by PCR amplification and sequencing of DNA barcodes. Finally, we describe the basic filtering and analysis steps of barcode sequencing data to ensure high-quality results.
- Published
- 2021
19. Neutrophil fluorescence in clozapine users is attributable to a 14kDa secretable protein
- Author
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Sera A. J. de With, Wai H. Man, Coen Maas, Maarten ten Berg, Wiepke Cahn, Arnold C. Koekman, Wouter W. van Solinge, and Tamar Tak
- Subjects
Cytochalasin B ,Neutrophils ,Azurophilic granule ,chemistry.chemical_compound ,Fluorescence microscope ,medicine ,Humans ,Platelet Activating Factor ,General Pharmacology, Toxicology and Pharmaceutics ,azurophilic granules ,Clozapine ,clozapine ,Degranulation ,Original Articles ,Subcellular localization ,Fluorescence ,Molecular biology ,Peptide Fragments ,Molecular Weight ,Luminescent Proteins ,Gene Expression Regulation ,Microscopy, Fluorescence ,Neurology ,chemistry ,Case-Control Studies ,Schizophrenia ,Neutrophil degranulation ,Original Article ,Electrophoresis, Polyacrylamide Gel ,Antipsychotic Agents ,medicine.drug - Abstract
Clozapine is the only antipsychotic agent with demonstrated efficacy in refractory schizophrenia. However, use of clozapine is hampered by its adverse effects, including potentially fatal agranulocytosis. Recently, we showed an association between neutrophil autofluorescence and clozapine use. In this study, we evaluated the subcellular localization of clozapine‐associated fluorescence and tried to elucidate its source. Neutrophils of clozapine users were analyzed with fluorescence microscopy to determine the emission spectrum and localization of the fluorescence signal. Next, these neutrophils were stimulated with different degranulation agents to determine the localization of fluorescence. Lastly, isolated neutrophil lysates of clozapine users were separated by SDS‐PAGE and evaluated. Clozapine‐associated fluorescence ranged from 420 nm to 720 nm, peaking at 500‐550 nm. Fluorescence was localized in a large number of small loci, suggesting granular localization of the signal. Neutrophil degranulation induced by Cytochalasin B/fMLF reduced fluorescence, whereas platelet‐activating factor (PAF)/fMLF induced degranulation did not, indicating that the fluorescence originates from a secretable substance in azurophilic granules. SDS‐PAGE of isolated neutrophil lysates revealed a fluorescent 14kDa band, suggesting that neutrophil fluorescence is likely to be originated from a 14kDa protein/peptide fragment. We conclude that clozapine‐associated fluorescence in neutrophils is originating from a 14kDa soluble protein (fragment) present in azurophilic granules of neutrophils. This protein could be an autofluorescent protein already present in the cell and upregulated by clozapine, or a protein altered by clozapine to express fluorescence. Future studies should further explore the identity of this protein and its potential role in the pathophysiology of clozapine‐induced agranulocytosis.
- Published
- 2020
20. Differential effects of short- and long-term treatment with mepolizumab on eosinophil kinetics in blood and sputum in eosinophilic asthma
- Author
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Leo Koenderman, Marwan Hassani, Saar Bendien van Nederveen, Corneli van Aalst, Nienke Vrisekoop, Kiki Tesselaar, and Tamar Tak
- Subjects
Science ,Immunology ,Placebo ,Article ,Respiratory medicine ,medicine ,Eosinopenia ,Eosinophilia ,Asthma ,Multidisciplinary ,business.industry ,Health sciences ,Drugs ,respiratory system ,Eosinophil ,medicine.disease ,medicine.anatomical_structure ,Clinical medicine ,Sputum ,medicine.symptom ,business ,Mepolizumab ,Homeostasis ,medicine.drug - Abstract
Summary Mepolizumab (anti-IL-5) is a successful biological for treatment of T2/eosinophilic asthma by blocking the IL-5-eosinophil axis. The kinetics of human eosinophils in blood and sputum was determined to better understand the underlying mechanism(s). Pulse-chase labeling was performed with 6,6-2H2-glucose in patients with asthma after short term (4 days) and long term (84 days) treatment with mepolizumab (n = 10) or placebo (n = 10). The retention time of eosinophils in sputum was longer than in blood. Treatment with mepolizumab induced a fast and long-lasting eosinopenia with no reduction of eosinophil progenitors. The retention time of eosinophils in blood was delayed only after short-term treatment. This leads to the hypothesis that IL-5 increases the number of IL-5-responsive progenitors and potentiates homing to the tissues, leading to reactive eosinophilia. Long-term treatment is associated with low numbers of IL-5-independent eosinophils in blood and tissues. Therefore, long-term treatment with mepolizumab restores the kinetics of eosinophils as normally found in homeostasis., Graphical abstract, Highlights • Anti-IL-5 (mepolizumab) treatment leads to inhibition of reactive eosinophilia • Reactive blood eosinophils have a high retention time in the absence of IL-5 • Eosinophils are long lived in the sputum of eosinophil asthmatics • Anti-IL-5 reduces proliferating progenitors rather than inhibiting differentiation, Health sciences; Immunology; Respiratory medicine; Clinical medicine; Drugs
- Published
- 2021
21. Simultaneous tracking of division and differentiation from individual hematopoietic stem and progenitor cells reveals within-family homogeneity despite population heterogeneity
- Author
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Tamar Tak, Ken R. Duffy, Noémie Paillon, Leïla Perié, Giulio Prevedello, and Gaël Simon
- Subjects
0303 health sciences ,education.field_of_study ,Cell type ,Offspring ,Population ,Biology ,Phenotype ,03 medical and health sciences ,Haematopoiesis ,0302 clinical medicine ,Evolutionary biology ,030220 oncology & carcinogenesis ,Identification (biology) ,Progenitor cell ,education ,030304 developmental biology ,Ancestor - Abstract
The advent of high throughput single cell methods such as scRNA-seq has uncovered substantial heterogeneity in the pool of hematopoietic stem and progenitor cells (HSPCs). A significant issue is how to reconcile those findings with the standard model of hematopoietic development, and a fundamental question is how much instruction is inherited by offspring from their ancestors. To address this, we further developed a high-throughput method that enables simultaneously determination of common ancestor, generation, and differentiation status of a large collection of single cells. Data from it revealed that while there is substantial population-level heterogeneity, cells that derived from a common ancestor were highly concordant in their division progression and share similar differentiation outcomes, revealing significant familial effects on both division and differentiation. Although each family diversifies to some extent, the overall collection of cell types observed in a population is largely composed of homogeneous families from heterogeneous ancestors. Heterogeneity between families could be explained, in part, by differences in ancestral expression of cell-surface markers that are used for phenotypic HSPC identification: CD48, SCA-1, c-kit and Flt3. These data call for a revision of the fundamental model of haematopoiesis from a single tree to an ensemble of trees from distinct ancestors where common ancestor effect must be considered. As HSPCs are cultured in the clinic before bone marrow transplantation, our results suggest that the broad range of engraftment and proliferation capacities of HSPCs could be consequences of the heterogeneity in their engrafted families, and altered culture conditions might reduce heterogeneity between families, possibly improving transplantation outcomes.
- Published
- 2019
22. Neutrophil-mediated Suppression of Influenza-induced Pathology Requires CD11b/CD18 (MAC-1)
- Author
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Okan W. Bastian, Louis Boon, Tamar Tak, Janesh Pillay, Linde Meyaard, Tomasz P. Rygiel, Leo Koenderman, Guruswamy Karnam, Marco C. Viveen, and Frank E. J. Coenjaerts
- Subjects
0301 basic medicine ,Pulmonary and Respiratory Medicine ,Pathology ,medicine.medical_specialty ,Adoptive cell transfer ,Time Factors ,Neutrophils ,T-Lymphocytes ,Clinical Biochemistry ,Macrophage-1 Antigen ,CD18 ,Mice, Transgenic ,Virus ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Antigen ,Orthomyxoviridae Infections ,Weight Loss ,medicine ,Animals ,Molecular Biology ,Lung ,CD11b Antigen ,biology ,business.industry ,Editorials ,Cell Biology ,Viral Load ,medicine.disease ,Adoptive Transfer ,Mice, Inbred C57BL ,Chemotaxis, Leukocyte ,Disease Models, Animal ,030104 developmental biology ,Integrin alpha M ,Influenza A virus ,CD18 Antigens ,Host-Pathogen Interactions ,biology.protein ,Female ,business ,Infiltration (medical) ,Viral load ,030215 immunology ,Signal Transduction - Abstract
Severe influenza virus infection can lead to life-threatening pathology through immune-mediated tissue damage. In various experimental models, this damage is dependent on T cells. There is conflicting evidence regarding the role of neutrophils in influenza-mediated pathology. Neutrophils are often regarded as cells causing tissue damage, but, in recent years, it has become clear that a subset of human neutrophils is capable of suppressing T cells, which is dependent on macrophage-1 antigen (CD11b/CD18). Therefore, we tested the hypothesis that immune suppression by neutrophils can reduce T cell-mediated pathology after influenza infection. Wild-type (WT) and CD11b-/- mice were infected with A/HK/2/68 (H3N2) influenza virus. Disease severity was monitored by weight loss, leukocyte infiltration, and immunohistochemistry. We demonstrated that CD11b-/- mice suffered increased weight loss compared with WT animals upon infection with influenza virus. This was accompanied by increased pulmonary leukocyte infiltration and lung damage. The exaggerated pathology in CD11b-/- mice was dependent on T cells, as it was reduced by T cell depletion. In addition, pathology in CD11b-/- mice was accompanied by higher numbers of T cells in the lungs early during infection compared with WT mice. Importantly, these differences in pathology were not associated with an increased viral load, suggesting that pathology was immune-mediated rather than caused by virus-induced damage. In contrast to adoptive transfer of CD11b-/- neutrophils, a single adoptive transfer of WT neutrophils partly restored protection against influenza-induced pathology, demonstrating the importance of neutrophil CD11b/CD18. Our data show that neutrophil CD11b/CD18 limits pathology in influenza-induced, T cell-mediated disease.
- Published
- 2017
23. Circulatory and maturation kinetics of human monocyte subsets in vivo
- Author
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Tamar Tak, Kiki Tesselaar, Rob J. de Boer, José A. M. Borghans, Julia Drylewicz, Leo Koenderman, Lennart Conemans, Pulmonologie, MUMC+: MA Med Staf Spec Longziekten (9), and RS: FHML non-thematic output
- Subjects
0301 basic medicine ,DNA Replication ,Male ,medicine.medical_specialty ,Cellular differentiation ,Immunology ,Lipopolysaccharide Receptors ,Biology ,GPI-Linked Proteins ,Biochemistry ,Models, Biological ,DENDRITIC CELLS ,Monocytes ,Immunophenotyping ,03 medical and health sciences ,Leukocyte Count ,0302 clinical medicine ,In vivo ,Reference Values ,Internal medicine ,Eosinophilia ,INFECTION ,medicine ,Homeostasis ,Humans ,MACROPHAGES ,Receptor ,Cellular Senescence ,Hematology ,Receptors, IgG ,PROLIFERATION ,Cell Differentiation ,Cell Biology ,Asthma ,Cell biology ,Kinetics ,030104 developmental biology ,medicine.anatomical_structure ,BLOOD MONOCYTES ,Circulatory system ,Female ,TURNOVER ,Bone marrow ,030215 immunology - Abstract
To the editor: Monocytes originate from the bone marrow (BM), are distributed in the bloodstream, and can differentiate in the tissue into skin macrophages or intestinal dendritic cells (DCs).[1][1] They play an essential role in the defense against pathogens[2][2] and are implicated in a range of
- Published
- 2017
24. Reversal of Sepsis-Like Features of Neutrophils by Interleukin-1 Blockade in Patients With Systemic-Onset Juvenile Idiopathic Arthritis
- Author
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Sytze de Roock, Thomas Vogl, Tamar Tak, Johannes Roth, Rianne C. Scholman, Leo Koenderman, Nienke M. ter Haar, Pieter H. C. Leliefeld, Wilco de Jager, Jenny Meerding, Anouk Verwoerd, Dirk Foell, Jorg van Loosdregt, Sebastiaan J. Vastert, and Michal Mokry
- Subjects
0301 basic medicine ,Male ,Neutrophils ,Immunology ,Arthritis ,Systemic inflammation ,Sepsis ,03 medical and health sciences ,Rheumatology ,medicine ,Immunology and Allergy ,Humans ,Prospective Studies ,Child ,Netherlands ,Anakinra ,Innate immune system ,business.industry ,Degranulation ,Interleukin ,medicine.disease ,Systemic-onset juvenile idiopathic arthritis ,Arthritis, Juvenile ,Systemic Inflammatory Response Syndrome ,Interleukin 1 Receptor Antagonist Protein ,030104 developmental biology ,Treatment Outcome ,Antirheumatic Agents ,Female ,medicine.symptom ,business ,medicine.drug - Abstract
Objective Neutrophils are the most abundant innate immune cells in the blood, but little is known about their role in (acquired) chronic autoinflammatory diseases. This study was undertaken to investigate the role of neutrophils in systemic-onset juvenile idiopathic arthritis (JIA), a prototypical multifactorial autoinflammatory disease that is characterized by arthritis and severe systemic inflammation. Methods Fifty patients with systemic-onset JIA who were receiving treatment with recombinant interleukin-1 receptor antagonist (rIL-1Ra; anakinra) were analyzed at disease onset and during remission. RNA sequencing was performed on fluorescence-activated cell-sorted neutrophils from 3 patients with active systemic-onset JIA and 3 healthy controls. Expression of activation markers, apoptosis, production of reactive oxygen species (ROS), and degranulation of secretory vesicles from neutrophils were assessed by flow cytometry in serum samples from 17 patients with systemic-onset JIA and 15 healthy controls. Results Neutrophil counts were markedly increased at disease onset, and this correlated with the levels of inflammatory mediators. The neutrophil counts normalized within days after the initiation of rIL-1Ra therapy. RNA-sequencing analysis revealed a substantial up-regulation of inflammatory processes in neutrophils from patients with active systemic-onset JIA, significantly overlapping with the transcriptome of sepsis. Correspondingly, neutrophils from patients with active systemic-onset JIA displayed a primed phenotype that was characterized by increased ROS production, CD62L shedding, and secretory vesicle degranulation, which was reversed by rIL-1Ra treatment in patients who had achieved clinical remission. Patients with a short disease duration had high neutrophil counts, more immature neutrophils, and a complete response to rIL-1Ra, whereas patients with symptoms for >1 month had normal neutrophil counts and an unsatisfactory response to rIL-1Ra. In vitro, rIL-1Ra antagonized the priming effect of IL-1β on neutrophils from healthy subjects. Conclusion These results strongly support the notion that neutrophils play an important role in systemic-onset JIA, especially in the early inflammatory phase of the disease. The findings also demonstrate that neutrophil numbers and the inflammatory activity of systemic-onset JIA are both susceptible to IL-1 blockade.
- Published
- 2017
25. The lung is a host defense niche for immediate neutrophil-mediated vascular protection
- Author
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Anton T.J. Tool, Björn Petri, Timo K. van den Berg, Jung Hwan Kim, Mark R. Looney, Leo Koenderman, Vivian G. Szeto, Matthew F. Krummel, Tamar Tak, Bryan G. Yipp, Ronald Lima, Paul Kubes, Lori Zbytnuik, Peter Pickkers, May Ho, Taco W. Kuijpers, Nick Swanlund, Pediatric surgery, Amsterdam Reproduction & Development (AR&D), Molecular cell biology and Immunology, ARD - Amsterdam Reproduction and Development, AII - Infectious diseases, Paediatric Infectious Diseases / Rheumatology / Immunology, Landsteiner Laboratory, AII - Amsterdam institute for Infection and Immunity, and CCA -Cancer Center Amsterdam
- Subjects
0301 basic medicine ,Endothelium ,genetic structures ,Immunology ,lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] ,Biology ,Article ,Vaccine Related ,Sepsis ,03 medical and health sciences ,0302 clinical medicine ,Downregulation and upregulation ,In vivo ,Biodefense ,medicine ,Journal Article ,Immunology and Allergy ,Receptor ,Lung ,ABL ,Prevention ,Hematology ,General Medicine ,respiratory system ,medicine.disease ,respiratory tract diseases ,Infectious Diseases ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,cardiovascular system ,Infection ,Intravital microscopy - Abstract
Bloodstream infection is a hallmark of sepsis, a medically emergent condition requiring rapid treatment. However, up-regulation of host defense proteins through Toll-like receptors (TLRs) and nuclear factor B requires hours after endotoxin detection. Using confocal pulmonary intravital microscopy, we identified that the lung provides a TLR4–Myd88 (myeloid differentiation primary response gene 88)–dependent and abl tyrosine kinase–dependent niche for immediate CD11b-dependent neutrophil responses to endotoxin and Gram-negative bloodstream pathogens. In an in vivo model of bacteremia, neutrophils crawled to and rapidly phagocytosed Escherichia coli sequestered to the lung endothelium. Therefore, the lung capillaries provide a vascular defensive niche whereby endothelium and neutrophils cooperate for immediate detection and capture of disseminating pathogens.
- Published
- 2017
26. What's your age again? Determination of human neutrophil half-lives revisited
- Author
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Leo Koenderman, Kiki Tesselaar, Janesh Pillay, José A. M. Borghans, and Tamar Tak
- Subjects
Human neutrophil ,Neutrophils ,Cell Cycle ,Immunology ,Immune regulation ,Bone Marrow Cells ,Cell Biology ,Biology ,Granulopoiesis ,medicine.anatomical_structure ,In vivo ,Circulatory system ,medicine ,Homeostasis ,Humans ,Immunology and Allergy ,Bone marrow ,Cellular Senescence ,Half-Life - Abstract
Neutrophils are the most abundant white blood cells and are indispensable for host defense. Recently, they have also been implicated in immune regulation and suppression. The latter functions seem hard to reconcile with the widely held view that neutrophils are very short-lived, with a circulatory half-life of
- Published
- 2013
27. Immune suppression by neutrophils and granulocytic myeloid-derived suppressor cells: similarities and differences
- Author
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Tamar Tak, Vera M. Kamp, Janesh Pillay, and Leo Koenderman
- Subjects
Immune regulation ,Immunological Synapses ,Neutrophils ,T cell ,Cellular differentiation ,Inflammation ,Review ,Cell Communication ,Biology ,Neutrophil Activation ,Immune tolerance ,Cellular and Molecular Neuroscience ,Immune system ,Immune Tolerance ,medicine ,Animals ,Humans ,Molecular Biology ,Pharmacology ,Effector ,Neutrophil ,Cell Differentiation ,Cell Biology ,Cell biology ,T-cell suppression ,Phenotype ,medicine.anatomical_structure ,Myeloid-derived suppressor cells ,Immunology ,Myeloid-derived Suppressor Cell ,Molecular Medicine ,Lymph Nodes ,medicine.symptom ,Reactive Oxygen Species ,Spleen ,Granulocytes - Abstract
Neutrophils are essential effector cells in the host defense against invading pathogens. Recently, novel neutrophil functions have emerged in addition to their classical anti-microbial role. One of these functions is the suppression of T cell responses. In this respect, neutrophils share similarities with granulocytic myeloid-derived suppressor cells (G-MDSCs). In this review, we will discuss the similarities and differences between neutrophils and G-MDSCs. Various types of G-MDSCs have been described, ranging from immature to mature cells shaping the immune response by different immune suppressive mechanisms. However, all types of G-MDSCs share distinct features of neutrophils, such as surface markers and morphology. We propose that G-MDSCs are heterogeneous and represent novel phenotypes of neutrophils, capable of suppressing the immune response. In this review, we will attempt to clarify the differences and similarities between neutrophils and G-MDSCs and attempt to facilitate further research.
- Published
- 2013
28. Human CD62L
- Author
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Tamar, Tak, Patrick, Wijten, Marjolein, Heeres, Peter, Pickkers, Arjen, Scholten, Albert J R, Heck, Nienke, Vrisekoop, Luke P, Leenen, José A M, Borghans, Kiki, Tesselaar, and Leo, Koenderman
- Subjects
Lipopolysaccharides ,Glucose ,Proteome ,Staining and Labeling ,Neutrophils ,Cluster Analysis ,Humans ,L-Selectin ,Deuterium ,Healthy Volunteers - Abstract
During acute inflammation, 3 neutrophil subsets are found in the blood: neutrophils with a conventional segmented nucleus, neutrophils with a banded nucleus, and T-cell-suppressing CD62L
- Published
- 2016
29. Similar activation state of neutrophils in sputum of asthma patients irrespective of sputum eosinophilia
- Author
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Bart Hilvering, Tamar Tak, Kiki Tesselaar, Leo Koenderman, and Pulmonary medicine
- Subjects
Antigens, Differentiation, T-Lymphocyte ,Male ,Pathology ,cell surface molecules ,B7-H1 Antigen ,Neutrophil Activation ,Leukocyte Count ,fluids and secretions ,neutrophils ,Immunology and Allergy ,Eosinophilia ,L-Selectin ,Non-U.S. Gov't ,Principal Component Analysis ,CD11b Antigen ,biology ,medicine.diagnostic_test ,Research Support, Non-U.S. Gov't ,Translational ,Degranulation ,Middle Aged ,Flow Cytometry ,medicine.anatomical_structure ,Integrin alpha M ,Female ,medicine.symptom ,Adult ,Granulocyte activation ,medicine.medical_specialty ,Cell Survival ,Immunology ,Research Support ,Flow cytometry ,lung ,Antigens, CD ,medicine ,Journal Article ,Humans ,Lectins, C-Type ,Aged ,Asthma ,Lung ,business.industry ,Sputum ,medicine.disease ,respiratory tract diseases ,Eosinophils ,biology.protein ,business - Abstract
Summary Inflammatory phenotypes of asthma are associated with differences in disease characteristics. It is unknown whether these inflammatory phenotypes are reflected by the activation status of neutrophils in blood and sputum. We obtained peripheral blood and induced sputum from 21 asthma patients and stratified our samples based on sputum eosinophilia resulting in two groups (>3% eosinophils: n = 13
- Published
- 2015
30. Differential antibacterial control by neutrophil subsets
- Author
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Janesh Pillay, Pieter H. C. Leliefeld, Luke P. H. Leenen, Nienke Vrisekoop, Taco W. Kuijpers, Suzan H.M. Rooijakkers, Matthijs Kox, Tamar Tak, Marjolein Heeres, Leo Koenderman, and Peter Pickkers
- Subjects
0301 basic medicine ,Hypersegmented neutrophil ,Male ,Methicillin-Resistant Staphylococcus aureus ,Adolescent ,Neutrophils ,Phagocytosis ,lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] ,Inflammation ,medicine.disease_cause ,GPI-Linked Proteins ,Phagolysosome ,Microbiology ,03 medical and health sciences ,Phagocytes, Granulocytes, and Myelopoiesis ,All institutes and research themes of the Radboud University Medical Center ,Phagosomes ,medicine ,Humans ,L-Selectin ,Child ,Pathogen ,chemistry.chemical_classification ,Reactive oxygen species ,Receptors, IgG ,Hematology ,030104 developmental biology ,chemistry ,Staphylococcus aureus ,Child, Preschool ,Acute Disease ,Female ,medicine.symptom ,Reactive Oxygen Species ,Intracellular - Abstract
Neutrophils comprise a heterogeneous population of cells essential for bacterial eradication, and defects in neutrophil function are associated with increased susceptibility to infection. In this study, neutrophils from healthy controls were shown to prevent bacterial proliferation for at least 48 hours when cocultured with methicillin-resistant Staphylococcus aureus (MRSA) in tissue-like scaffolds by establishing a bacteriostatic environment inside their phagolysosome. This intracellular bacterial containment is independent of reactive oxygen species because neutrophils that lack a functional nicotinamide adenine dinucleotide phosphate-oxidase complex displayed no defect in intracellular bacterial containment, whereas killing of the pathogen was impaired. During acute inflammation, a subset of CD16bright/CD62Ldim hypersegmented neutrophils displayed normal phagocytosis associated with a remarkably poor capacity to contain bacteria intracellularly. Conversely, CD16dim-banded neutrophils were the only neutrophil subset that adequately contained MRSA. These findings demonstrate a clear neutrophil heterogeneity in their antimicrobial capacity and the appearance of neutrophil subsets with a clear differentiation in functionality during acute inflammation. Furthermore, this study provides an evolutionary basis for the rapid release of banded neutrophils into the circulation during acute inflammation.
- Published
- 2018
31. Monocytes and neutrophils in the inflammatory cascade of systemic onset Juvenile Idiopathic Arthritis
- Author
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N ter Haar, Tamar Tak, Pieter H. C. Leliefeld, Bas Vastert, W. de Jager, Rianne C. Scholman, and S. de Roock
- Subjects
medicine.medical_specialty ,education ,Familial Mediterranean fever ,Pediatrics ,Rheumatology ,International congress ,Internal medicine ,medicine ,Immunology and Allergy ,Pediatrics, Perinatology, and Child Health ,Autoinflammatory disease ,health care economics and organizations ,business.industry ,social sciences ,medicine.disease ,Perinatology ,humanities ,Systemic-onset juvenile idiopathic arthritis ,and Child Health ,Specific granule ,Pediatrics, Perinatology and Child Health ,Immunology ,Inflammatory cascade ,Oral Presentation ,business ,geographic locations - Abstract
8th International Congress of Familial Mediterranean Fever and Systemic Autoinflammatory Diseases
- Published
- 2015
32. Monocyte Subsets Are Differentially Lost from the Circulation during Acute Inflammation Induced by Human Experimental Endotoxemia
- Author
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Tamar Tak, Roger van Groenendael, Leo Koenderman, and Peter Pickkers
- Subjects
Adult ,Lipopolysaccharides ,Male ,0301 basic medicine ,Chemokine ,Lipopolysaccharide ,CD14 ,lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] ,Lipopolysaccharide Receptors ,Cell Count ,CCL4 ,CD16 ,CCL2 ,Monocyte ,Monocytes ,Young Adult ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Sepsis ,medicine ,Journal Article ,Humans ,Immunology and Allergy ,CX3CL1 ,Acute inflammation ,Inflammation ,biology ,Chemistry ,Receptors, IgG ,Cell Differentiation ,Healthy Volunteers ,Endotoxemia ,Systemic inflammatory response syndrome ,030104 developmental biology ,medicine.anatomical_structure ,Blood Circulation ,Immunology ,biology.protein ,Chemokines ,030215 immunology - Abstract
Three human monocyte subsets are recognized with different functions in the immune system: CD14++/CD16- classical monocytes (CM), CD14++/CD16+ intermediate monocytes (IM) and CD14+/CD16++ non-classical monocytes (NCM). Increased IM and NCM percentages have been reported under inflammatory conditions, yet little is known about monocyte subsets at the onset of inflammation. The human endotoxemia model is uniquely capable of studying the first phases of acute inflammation induced by intravenous injection of 2 ng/kg bodyweight lipopolysaccharide (LPS) into healthy volunteers. After that, monocyte subset counts, activation/differentiation status and chemokine levels were studied over 24 h. The numbers of all subsets were decreased by >95% after LPS injection. CM numbers recovered first (3- 6 h), followed by IM (6-8 h) and NCM numbers (8-24 h). Similarly, increased monocyte counts were observed first in CM (8 h), followed by IM and NCM (24 h). Monocytes did not display a clear activated phenotype (minor increase in CD11b and CD38 expression). Plasma levels of CCL2, CCL4 and CX3CL1 closely resembled the cell numbers of CM, IM and NCM, respectively. Our study provides critical insights into the earliest stages of acute inflammation and emphasizes the necessity to stain for different monocyte subsets when studying the role of monocytes in disease, as neither function nor kinetics of the subsets overlap.
- Published
- 2017
33. A1.06 Phagocyte involvement in systemic onset juvenile idiopathic arthritis
- Author
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Tamar Tak, Jenny Meerding, SJ Vastert, W. de Jager, N ter Haar, Phc Leliefeld, RS Scholman, and S. de Roock
- Subjects
0301 basic medicine ,Chemokine ,medicine.medical_treatment ,Immunology ,Arthritis ,Peripheral blood mononuclear cell ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,0302 clinical medicine ,Rheumatology ,medicine ,Immunology and Allergy ,030203 arthritis & rheumatology ,CD64 ,biology ,business.industry ,Monocyte ,Interleukin ,medicine.disease ,Systemic-onset juvenile idiopathic arthritis ,030104 developmental biology ,Cytokine ,medicine.anatomical_structure ,biology.protein ,business - Abstract
Background Systemic onset Juvenile Idiopathic Artritis (sJIA) is a systemic autoinflammatory disease, characterised by arthritis, spiking fever and rash and elevation of serum S100-proteins and interleukin (IL)-18. The role of monocytes and neutrophils in the inflammatory cascade of sJIA is still unclear. Objective To study the role of monocytes and neutrophils in the inflammatory cascade of sJIA. Methods We determined neutrophil activation ex vivo (phenotype and cell membrane markers) and after stimulation (ROS-production and degranulation) of cells derived from sJIA with disease onset or in remission, compared to healthy donors (HDs). To investigate the role of monocytes, we assessed cytokine production of PBMCs from sJIA patients and HDs after stimulation with TLR-4 activating S100-proteins (+/- ATP) or other TLR-ligands. In a cohort of sJIA patients at onset and during inactive disease, we evaluated cell counts and serum levels of cytokines, chemokines and other analytes. Cytokine concentrations in supernatant and serum were determined by multiplex immunoassay. Results Twenty-one of 23 patients with onset sJIA had elevated neutrophil counts, while monocyte counts were elevated in only 5/23 patients. Many inflammatory markers were significantly elevated in serum of onset sJIA patients, among which several neutrophil specific proteins indicating the importance of this cell type. Neutrophils from onset sJIA patients showed an activated phenotype, reflected by higherex vivocell membraneexpression of FC-gamma receptors (CD32 and CD64), markers of secretory vesicles (CD35) and specific granules (CD66b). ROS production and degranulation were also enhanced in onset sJIA. Neutrophil phenotypenormalized when patients were in remission. In contrast to the hyperactivated status of neutrophils in active sJIA, PBMCs from these patients produced less Il-1b, IL-18, IL-6 and TNF-a upon TLR-stimulation compared to PBMCs from remission patients or HDs, suggesting tolerance after exposure to high TLR4 stimulating S100-levels in vivo. Conclusions We show here that monocytes from onset sJIA patients produce less cytokines upon stimulation, while the neutrophils are hyperactivated, reflected by increased cell membrane activation markers, ROS production and degranulation. The exact role of each cell type and activity and their interaction in sJIA pathology is currently under investigation.
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- 2016
34. A subset of neutrophils in human systemic inflammation inhibits T cell responses through Mac-1
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Luke P. H. Leenen, Tamar Tak, Tjaakje Visser, Janesh Pillay, Laurien H. Ulfman, Vera M. Kamp, Leo Koenderman, Jan-Willem J. Lammers, Els van Hoffen, and Peter Pickkers
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Lipopolysaccharides ,Immunological Synapses ,Neutrophils ,T cell ,T-Lymphocytes ,Population ,Iron metabolism Pathogenesis and modulation of inflammation [IGMD 7] ,Macrophage-1 Antigen ,Inflammation ,Biology ,Systemic inflammation ,Lymphocyte Activation ,Immune tolerance ,Immunological synapse ,Immune system ,medicine ,Immune Tolerance ,Animals ,Humans ,education ,Autoimmune disease ,education.field_of_study ,General Medicine ,medicine.disease ,Coculture Techniques ,medicine.anatomical_structure ,Immunology ,Injections, Intravenous ,medicine.symptom ,Reactive Oxygen Species ,Research Article - Abstract
Contains fulltext : 108037.pdf (Publisher’s version ) (Open Access) Suppression of immune responses is necessary to limit damage to host tissue during inflammation, but it can be detrimental in specific immune responses, such as sepsis and antitumor immunity. Recently, immature myeloid cells have been implicated in the suppression of immune responses in mouse models of cancer, infectious disease, bone marrow transplantation, and autoimmune disease. Here, we report the identification of a subset of mature human neutrophils (CD11cbright/CD62Ldim/CD11bbright/CD16bright) as what we believe to be a unique circulating population of myeloid cells, capable of suppressing human T cell proliferation. These cells were observed in humans in vivo during acute systemic inflammation induced by endotoxin challenge or by severe injury. Local release of hydrogen peroxide from the neutrophils into the immunological synapse between the neutrophils and T cells mediated the suppression of T cell proliferation and required neutrophil expression of the integrin Mac-1 (alphaMbeta2). Our data demonstrate that suppression of T cell function can be accomplished by a subset of human neutrophils that can be systemically induced in response to acute inflammation. Identification of the pivotal role of neutrophil Mac-1 and ROS in this process provides a potential target for modulating immune responses in humans.
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- 2012
35. OP0196 The Role of Neutrophils in the Inflammatory Cascade of Systemic Onset Juvenile Idiopathic Arthritis
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N ter Haar, Tamar Tak, Bas Vastert, and S. de Roock
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Hypersegmented neutrophil ,business.industry ,medicine.medical_treatment ,Immunology ,Elastase ,Degranulation ,Interleukin ,CD16 ,medicine.disease ,Peripheral blood mononuclear cell ,General Biochemistry, Genetics and Molecular Biology ,Systemic-onset juvenile idiopathic arthritis ,Cytokine ,Rheumatology ,Immunology and Allergy ,Medicine ,business - Abstract
Background Systemic onset Juvenile Idiopathic Artritis (sJIA) is considered an autoinflammatory disease, with increased circulating neutrophil counts and extremely high serum levels of S100 proteins and interleukin (IL)-18. We have previously shown that upon stimulation with S100 proteins and ATP, peripheral blood mononuclear cells (PBMCs) of healthy donors produce high levels of IL-1β and IL-18; however this cytokine production is decreased in PBMCs of sJIA patients with active disease and partly restored when patients are in remission. 1 Given the observed hyporesponsiveness of PBMCs from sJIA patients, we hypothesized that neutrophils might play an important role in the inflammatory cascade of sJIA. Objectives Our objective was to investigate the role of neutrophils in sJIA, with a focus on the relation between neutrophils, S100 proteins and IL-18. Methods We determined ex vivo cell frequencies of patients at disease onset, patients with inactive disease and healthy controls by flow cytometric analysis, using fluorescent beads for absolute counts. Neutrophils from healthy donors were sorted and subsequently primed with S100 proteins in a time series up to 20 hours with or without Formyl-Methionyl-Leucyl-Phenylalanine (fMLP) for the last 10 minutes. Elastase and cytokine levels in supernatant were measured by Luminex, neutrophil activation markers were analysed by flow cytometry. Results Patients with new onset sJIA had significantly elevated neutrophil counts compared to healthy controls and patients with inactive disease. Immature neutrophils (CD16 dim CD62L + ) and normally matured neutrophils (CD16 + CD62L + ) were significantly higher in patients with new onset sJIA compared to healthy controls or patients with inactive disease, while hypersegmented neutrophils (CD16 + CD62L dim ) were comparable between patients and controls. Given the high serum levels of S100 proteins in active sJIA, we investigated if neutrophils could be activated by these proteins. Priming with S100A9 before stimulation with fMLP increased activation and degranulation of specific granules and secretory vesicles compared to unprimed cells. This was reflected by an increased expression of CD11b, CD66b and CD35. Upon stimulation with S100A9, we observed an increase in elastase secretion in the culture supernatant, as well as a minor increase in IL-6, IL-18 and TNF-α. Conclusions Patients with new onset sJIA have increased neutrophil counts. S100 proteins prime neutrophils and enhance degranulation upon a second stimulus such as fMLP. We are now exploring whether IL-18 or other pro-inflammatory mediators elevated in sJIA plasma can also prime neutrophils. Further, we will investigate whether ex vivo neutrophils from sJIA patients are more activated or respond differently to stimulation compared to patients with inactive disease or healthy controls. References N. Ter Haar, D. Holzinger, W. de Jager, R. Scholman, S. de Roock, B. Vastert. IL-18 production upon s100 stimulation is reduced in active sJIA patients compared to sJIA patients in remission and healthy controls. Pediatric Rheumatology 2014, 12(Suppl 1):O24 Acknowledgements We would like to acknowledge D. Holzinger, T. Vogl, D. Foell and J. Roth for providing the S100 proteins. Disclosure of Interest None declared
- Published
- 2015
36. Similar activation of sputum granulocytes in eosinophilic and non-eosinophilic asthma
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Tamar Tak, Leo Koenderman, Kiki Tesselaar, and Bart Hilvering
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Pulmonary and Respiratory Medicine ,Allergy ,medicine.diagnostic_test ,business.industry ,Immunology ,Degranulation ,Eosinophilic asthma ,SPUTUM EOSINOPHILIA ,medicine.disease ,Bioinformatics ,respiratory tract diseases ,Flow cytometry ,fluids and secretions ,Eosinophilic ,medicine ,Immunology and Allergy ,Sputum ,Oral Presentation ,medicine.symptom ,business ,Asthma - Abstract
Method We obtained peripheral blood and induced sputum from 21 asthma patients and defined two patient groups based on sputum eosinophilia (cut-off 3%). Eosinophils and neutrophils from blood and sputum were analysed by flow cytometry for expression of activation and degranulation markers. Data were analysed by both classical, non-parametric statistics and a more advanced multi-dimensional approach, using principal component analysis (PCA).
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- 2015
37. Erythropoietin directly remodels the clonal composition of murine hematopoietic multipotent progenitor cells
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Almut S Eisele, Jason Cosgrove, Aurelie Magniez, Emilie Tubeuf, Sabrina Tenreira Bento, Cecile Conrad, Fanny Cayrac, Tamar Tak, Anne-Marie Lyne, Jos Urbanus, and Leïla Perié
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Cell ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Downregulation and upregulation ,hemic and lymphatic diseases ,medicine ,Animals ,Erythropoiesis ,Progenitor cell ,Erythropoietin ,030304 developmental biology ,Progenitor ,0303 health sciences ,General Immunology and Microbiology ,Multipotent Stem Cells ,General Neuroscience ,Cell Differentiation ,General Medicine ,Hematopoietic Stem Cells ,3. Good health ,Cell biology ,Transplantation ,Haematopoiesis ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Ex vivo ,medicine.drug - Abstract
The cytokine erythropoietin (EPO) is a potent inducer of erythrocyte development and one of the most prescribed biopharmaceuticals. The action of EPO on erythroid progenitor cells is well established, but its direct action on hematopoietic stem and progenitor cells (HSPCs) is still debated. Here, using cellular barcoding, we traced the differentiation of hundreds of single murine HSPCs, after ex vivo EPO-exposure and transplantation, in five different hematopoietic cell lineages, and observed the transient occurrence of high-output Myeloid-Erythroid-megaKaryocyte (MEK)-biased and Myeloid-B-cell-Dendritic cell (MBDC)-biased clones. Single-cell RNA sequencing (ScRNAseq) analysis of ex vivo EPO-exposed HSPCs revealed that EPO induced the upregulation of erythroid associated genes in a subset of HSPCs, overlapping with multipotent progenitor (MPP) 1 and MPP2. Transplantation of Barcoded EPO-exposed-MPP2 confirmed their enrichment in Myeloid-Erythroid-biased clones. Collectively, our data show that EPO does act directly on MPP independent of the niche, and modulates fate by remodeling the clonal composition of the MPP pool.
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