title: Gut Microbiota Regulates K/BxN Autoimmune Arthritis through Follicular Helper T but Not Th17 Cells.
abstract: The bacterial community that colonizes mucosal surfaces helps shape the development and function of the immune system. The K/BxN autoimmune arthritis model is dependent on the microbiota, and particularly on segmented filamentous bacteria, for the autoimmune phenotype. The mechanisms of how the gut microbiota affects arthritis development are not well understood. In this study, we investigate the contribution of two T cell subsets, Th17 and follicular helper T (Tfh), to arthritis and how microbiota modulates their differentiation. Using genetic approaches, we demonstrate that IL-17 is dispensable for arthritis. Antibiotic treatment inhibits disease in IL-17-deficient animals, suggesting that the gut microbiota regulates arthritis independent of Th17 cells. In contrast, conditional deletion of Bcl6 in T cells blocks Tfh cell differentiation and arthritis development. Furthermore, Tfh cell differentiation is defective in antibiotic-treated mice. Taken together, we conclude that gut microbiota regulates arthritis through Tfh but not Th17 cells. These findings have implications in our understanding of how environmental factors contribute to the development of autoimmune diseases.
authors.affiliation: Committee on Immunology, University of Chicago, Chicago, IL 60637; Section of Rheumatology, Department of Medicine, University of Chicago, Chicago, IL 60637; Knapp Center for Lupus and Immunology Research, University of Chicago, Chicago, IL 60637;
authors.forename: Katharine E
authors.initials: KE
authors.lastname: Block
authors.affiliation: Section of Rheumatology, Department of Medicine, University of Chicago, Chicago, IL 60637; Knapp Center for Lupus and Immunology Research, University of Chicago, Chicago, IL 60637;
authors.forename: Zhong
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202; and.
authors.forename: Alexander L
authors.initials: AL
authors.lastname: Dent
authors.affiliation: Committee on Immunology, University of Chicago, Chicago, IL 60637; Department of Pathology, University of Chicago, Chicago, IL 60637.
authors.forename: Barbara L
authors.initials: BL
authors.lastname: Kee
authors.affiliation: Committee on Immunology, University of Chicago, Chicago, IL 60637; Section of Rheumatology, Department of Medicine, University of Chicago, Chicago, IL 60637; Knapp Center for Lupus and Immunology Research, University of Chicago, Chicago, IL 60637; hhuang@bsd.uchicago.edu.
authors.forename: Haochu
authors.initials: H
authors.lastname: Huang
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000382:microbiology*; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics; D004195:Disease Models, Animal; D000069196:Gastrointestinal Microbiome / Q000276:immunology*; D018858:Germinal Center / Q000166:cytology / Q000276:immunology; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D009092:Mucous Membrane / Q000166:cytology / Q000276:immunology; D051560:Proto-Oncogene Proteins c-bcl-6; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*
chemical_list: C490010:Bcl6 protein, mouse; D004268:DNA-Binding Proteins; D051560:Proto-Oncogene Proteins c-bcl-6