title: A subpopulation of high IL-21-producing CD4(+) T cells in Peyer's Patches is induced by the microbiota and regulates germinal centers.
abstract: The production of IL-21 by T follicular helper (Tfh) cells is vital in driving the germinal centre reaction and high affinity antibody formation. However, the degree of Tfh cell heterogeneity and function is not fully understood. We used a novel IL-21eGFP reporter mouse strain to analyze the diversity and role of Tfh cells. Through the analysis of GFP expression in lymphoid organs of IL-21eGFP mice, we identified a subpopulation of GFP(+), high IL-21 producing Tfh cells present only in Peyer's Patches. GFP(+)Tfh cells were found to be polyclonal and related to GFP(-)Tfh cells of Peyer's Patches in TCR repertoire composition and overall gene expression. Studies on the mechanisms of induction of GFP(+)Tfh cells demonstrated that they required the intestinal microbiota and a diverse repertoire of CD4(+) T cells and B cells. Importantly, ablation of GFP(+) cells resulted in a reduced frequency of Peyer's Patches IgG1 and germinal center B cells in addition to small but significant shifts in gut microbiome composition. Our work highlights the diversity among IL-21 producing CD4(+) Tfh cells, and the interrelationship between the intestinal bacteria and Tfh cell responses in the gut.
authors: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore.
authors: Leigh
authors: L
authors: Jones
authors: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore.
authors: Wen Qi
authors: WQ
authors: Ho
authors: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore.|Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors: Sze
authors: S
authors: Ying
authors: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore.
authors: Lakshmi
authors: L
authors: Ramakrishna
authors: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore.
authors: Kandhadayar G
authors: KG
authors: Srinivasan
authors: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore.
authors: Marina
authors: M
authors: Yurieva
authors: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore.|School of Biological Sciences, Nanyang Technological University, Singapore.
authors: Wan Pei
authors: WP
authors: Ng
authors: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore.
authors: Sharrada
authors: S
authors: Subramaniam
authors: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore.
authors: Nur H
authors: NH
authors: Hamadee
authors: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore.
authors: Sabrina
authors: S
authors: Joseph
authors: Skirball Institute and Department of Pathology, New York University School of Medicine, New York, NY, USA.
authors: Jayashree
authors: J
authors: Dolpady
authors: Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, and RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Japan.
authors: Koji
authors: K
authors: Atarashi
authors: Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, and RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Japan.
authors: Kenya
authors: K
authors: Honda
authors: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore.
authors: Francesca
authors: F
authors: Zolezzi
authors: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore.
authors: Michael
authors: M
authors: Poidinger
authors: Skirball Institute and Department of Pathology, New York University School of Medicine, New York, NY, USA.
authors: Juan J
authors: JJ
authors: Lafaille
authors: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore.|Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine and Department of Cell Biology, New York University School of Medicine, New York, NY, USA.
authors: Maria A
authors: MA
authors: Curotto de Lafaille
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002478:Cells, Cultured; D000069196:Gastrointestinal Microbiome; D018858:Germinal Center / Q000276:immunology* / Q000382:microbiology; D007378:Interleukins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D010581:Peyer's Patches / Q000166:cytology / Q000276:immunology* / Q000382:microbiology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D000098546:Interleukin-21
chemical_list: D007378:Interleukins; D000098546:Interleukin-21