title: Focused specificity of intestinal TH17 cells towards commensal bacterial antigens.
abstract: T-helper-17 (TH17) cells have critical roles in mucosal defence and in autoimmune disease pathogenesis. They are most abundant in the small intestine lamina propria, where their presence requires colonization of mice with microbiota. Segmented filamentous bacteria (SFB) are sufficient to induce TH17 cells and to promote TH17-dependent autoimmune disease in animal models. However, the specificity of TH17 cells, the mechanism of their induction by distinct bacteria, and the means by which they foster tissue-specific inflammation remain unknown. Here we show that the T-cell antigen receptor (TCR) repertoire of intestinal TH17 cells in SFB-colonized mice has minimal overlap with that of other intestinal CD4(+) T cells and that most TH17 cells, but not other T cells, recognize antigens encoded by SFB. T cells with antigen receptors specific for SFB-encoded peptides differentiated into RORγt-expressing TH17 cells, even if SFB-colonized mice also harboured a strong TH1 cell inducer, Listeria monocytogenes, in their intestine. The match of T-cell effector function with antigen specificity is thus determined by the type of bacteria that produce the antigen. These findings have significant implications for understanding how commensal microbiota contribute to organ-specific autoimmunity and for developing novel mucosal vaccines.
authors.affiliation: The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, New York 10016, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.affiliation: The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, New York 10016, USA.
authors.forename: Miriam B
authors.initials: MB
authors.lastname: Torchinsky
authors.affiliation: The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, New York 10016, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Gobert
authors.affiliation: The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, New York 10016, USA.
authors.forename: Huizhong
authors.initials: H
authors.lastname: Xiong
authors.affiliation: The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, New York 10016, USA.
authors.forename: Mo
authors.initials: M
authors.lastname: Xu
authors.affiliation: 1] Department of Microbiology, Center for Immunology, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA [2] Mucosal Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-0485, USA.
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Linehan
authors.affiliation: Department of Microbiology, New York University School of Medicine, New York, New York 10016, USA.
authors.forename: Francis
authors.initials: F
authors.lastname: Alonzo
authors.affiliation: The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, New York 10016, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Ng
authors.affiliation: The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, New York 10016, USA.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Chen
authors.affiliation: The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, New York 10016, USA.
authors.forename: Xiyao
authors.initials: X
authors.lastname: Lin
authors.affiliation: The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, New York 10016, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Sczesnak
authors.affiliation: The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, New York 10016, USA.
authors.forename: Jia-Jun
authors.initials: JJ
authors.lastname: Liao
authors.affiliation: Department of Microbiology, New York University School of Medicine, New York, New York 10016, USA.
authors.forename: Victor J
authors.initials: VJ
authors.lastname: Torres
authors.affiliation: Department of Microbiology, Center for Immunology, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA.
authors.forename: Marc K
authors.initials: MK
authors.lastname: Jenkins
authors.affiliation: The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, New York 10016, USA.
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Lafaille
authors.affiliation: 1] The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, New York 10016, USA [2] Howard Hughes Medical Institute, New York University School of Medicine, New York, New York 10016, USA.
authors.forename: Dan R
authors.initials: DR
authors.lastname: Littman
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000737:chemistry / Q000276:immunology*; D001428:Bacterial Vaccines; D002454:Cell Differentiation; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology; D006094:Gram-Positive Bacteria / Q000737:chemistry / Q000276:immunology*; D006825:Hybridomas / Q000276:immunology; D018928:Immunity, Mucosal / Q000276:immunology; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology; D007421:Intestine, Small / Q000166:cytology / Q000276:immunology; D007422:Intestines / Q000166:cytology / Q000276:immunology*; D008089:Listeria monocytogenes / Q000276:immunology; D051379:Mice; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013559:Symbiosis; D058504:Th17 Cells / Q000166:cytology / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial; D001428:Bacterial Vaccines; D018984:Epitopes, T-Lymphocyte; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D011948:Receptors, Antigen, T-Cell
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