Immunity
Volume 32, Issue 6, 25 June 2010, Pages 815-827
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Article
Gut-Residing Segmented Filamentous Bacteria Drive Autoimmune Arthritis via T Helper 17 Cells

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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.

Highlights

► Commensal microbes drive arthritis development in the K/BxN mouse model ► Germ-free mice had deficits in gut and spleen Th17 cells and in serum autoantibodies ► IL-17 blockade could prevent arthritis through a direct effect on splenic B cells ► Segmented filamentous bacteria could alone trigger arthritis in germ-free K/BxN mice

CELLIMMUNO
MOLIMMUNO
MICROBIO

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