title: Gut-residing segmented filamentous bacteria drive autoimmune arthritis via T helper 17 cells.
abstract: Commensal microbes can have a substantial impact on autoimmune disorders, but the underlying molecular and cellular mechanisms remain largely unexplored. We report that autoimmune arthritis was strongly attenuated in the K/BxN mouse model under germ-free (GF) conditions, accompanied by reductions in serum autoantibody titers, splenic autoantibody-secreting cells, germinal centers, and the splenic T helper 17 (Th17) cell population. Neutralization of interleukin-17 prevented arthritis development in specific-pathogen-free K/BxN mice resulting from a direct effect of this cytokine on B cells to inhibit germinal center formation. The systemic deficiencies of the GF animals reflected a loss of Th17 cells from the small intestinal lamina propria. Introduction of a single gut-residing species, segmented filamentous bacteria, into GF animals reinstated the lamina propria Th17 cell compartment and production of autoantibodies, and arthritis rapidly ensued. Thus, a single commensal microbe, via its ability to promote a specific Th cell subset, can drive an autoimmune disease.
authors.affiliation: Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Hsin-Jung
authors.initials: HJ
authors.lastname: Wu
authors.forename: Ivaylo I
authors.initials: II
authors.lastname: Ivanov
authors.forename: Jaime
authors.initials: J
authors.lastname: Darce
authors.forename: Kimie
authors.initials: K
authors.lastname: Hattori
authors.forename: Tatsuichiro
authors.initials: T
authors.lastname: Shima
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Umesaki
authors.forename: Dan R
authors.initials: DR
authors.lastname: Littman
authors.forename: Christophe
authors.initials: C
authors.lastname: Benoist
authors.forename: Diane
authors.initials: D
authors.lastname: Mathis
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology / Q000382:microbiology; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000382:microbiology; D001419:Bacteria / Q000276:immunology*; D002469:Cell Separation; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D020381:Interleukin-17 / Q000276:immunology*; D007422:Intestines / Q000382:microbiology*; D051379:Mice; D020133:Reverse Transcriptase Polymerase Chain Reaction; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
chemical_list: D020381:Interleukin-17