title: Foxp3(+) T cells regulate immunoglobulin a selection and facilitate diversification of bacterial species responsible for immune homeostasis.
abstract: Foxp3(+) T cells play a critical role for the maintenance of immune tolerance. Here we show that in mice, Foxp3(+) T cells contributed to diversification of gut microbiota, particularly of species belonging to Firmicutes. The control of indigenous bacteria by Foxp3(+) T cells involved regulatory functions both outside and inside germinal centers (GCs), consisting of suppression of inflammation and regulation of immunoglobulin A (IgA) selection in Peyer's patches, respectively. Diversified and selected IgAs contributed to maintenance of diversified and balanced microbiota, which in turn facilitated the expansion of Foxp3(+) T cells, induction of GCs, and IgA responses in the gut through a symbiotic regulatory loop. Thus, the adaptive immune system, through cellular and molecular components that are required for immune tolerance and through the diversification as well as selection of antibody repertoire, mediates host-microbial symbiosis by controlling the richness and balance of bacterial communities required for homeostasis.
authors.affiliation: Laboratory for Mucosal Immunity, Center for Integrative Medical Sciences (IMS-RCAI), RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi, Yokohama, 230-0045 Kanagawa, Japan.
authors.forename: Shimpei
authors.initials: S
authors.lastname: Kawamoto
authors.affiliation: Laboratory for Mucosal Immunity, Center for Integrative Medical Sciences (IMS-RCAI), RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi, Yokohama, 230-0045 Kanagawa, Japan.
authors.forename: Mikako
authors.initials: M
authors.lastname: Maruya
authors.affiliation: Laboratory for Mucosal Immunity, Center for Integrative Medical Sciences (IMS-RCAI), RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi, Yokohama, 230-0045 Kanagawa, Japan.
authors.forename: Lucia M
authors.initials: LM
authors.lastname: Kato
authors.affiliation: Center for Omics and Bioinformatics, Graduate School of Frontier Sciences, The University of Tokyo, 5-1-5 Kashiwa-no-ha, Kashiwa, 277-8561 Chiba, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Suda
authors.affiliation: Laboratory for Gut Homeostasis, Center for Integrative Medical Sciences (IMS-RCAI), RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi, Yokohama, 230-0045 Kanagawa, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Atarashi
authors.affiliation: Laboratory for Mucosal Immunity, Center for Integrative Medical Sciences (IMS-RCAI), RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi, Yokohama, 230-0045 Kanagawa, Japan.
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Doi
authors.affiliation: Laboratory for Mucosal Immunity, Center for Integrative Medical Sciences (IMS-RCAI), RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi, Yokohama, 230-0045 Kanagawa, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Tsutsui
authors.affiliation: Laboratory for Mucosal Immunity, Center for Integrative Medical Sciences (IMS-RCAI), RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi, Yokohama, 230-0045 Kanagawa, Japan; Department of Medical Genetics and Developmental Biology, 4(th) Military Medical University, Chang-Le Xi Street #17, Xi'an 710032, China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Qin
authors.affiliation: Laboratory for Gut Homeostasis, Center for Integrative Medical Sciences (IMS-RCAI), RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi, Yokohama, 230-0045 Kanagawa, Japan.
authors.forename: Kenya
authors.initials: K
authors.lastname: Honda
authors.affiliation: Laboratory for Tissue Dynamics, Center for Integrative Medical Sciences (IMS-RCAI), RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi, Yokohama, 230-0045 Kanagawa, Japan.
authors.forename: Takaharu
authors.initials: T
authors.lastname: Okada
authors.affiliation: Center for Omics and Bioinformatics, Graduate School of Frontier Sciences, The University of Tokyo, 5-1-5 Kashiwa-no-ha, Kashiwa, 277-8561 Chiba, Japan.
authors.forename: Masahira
authors.initials: M
authors.lastname: Hattori
authors.affiliation: Laboratory for Mucosal Immunity, Center for Integrative Medical Sciences (IMS-RCAI), RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi, Yokohama, 230-0045 Kanagawa, Japan. Electronic address: sidonia-f@rcai.riken.jp.
authors.forename: Sidonia
authors.initials: S
authors.lastname: Fagarasan
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D051858:Forkhead Transcription Factors / Q000276:immunology; D041981:Gastrointestinal Tract / Q000276:immunology* / Q000382:microbiology*; D005856:Germ-Free Life; D018858:Germinal Center / Q000276:immunology; D018398:Homeodomain Proteins / Q000235:genetics; D006706:Homeostasis / Q000276:immunology; D007108:Immune Tolerance / Q000276:immunology; D007070:Immunoglobulin A / Q000276:immunology*; D007249:Inflammation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016513:Mice, SCID / Q000382:microbiology; D064307:Microbiota / Q000276:immunology*; D010581:Peyer's Patches / Q000276:immunology; D013559:Symbiosis / Q000276:immunology
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D018398:Homeodomain Proteins; D007070:Immunoglobulin A; C064658:RAG-1 protein