Gut-Residing Segmented Filamentous Bacteria Drive Autoimmune Arthritis via T Helper 17 Cells.
Wu, Hsin-Jung 1,2; Ivanov, Ivaylo I. 3; Darce, Jaime 1,2; Hattori, Kimie 1,2; Shima, Tatsuichiro 5; Umesaki, Yoshinori 5; Littman, Dan R. 3,4; Benoist, Christophe 1,2,6,*; Mathis, Diane 1,2,6,*
[Article]
Immunity.
32(6):815-827, June 2010.
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SUMMARY: 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.
(C) 2010Elsevier, Inc.