Gut-residing segmented filamentous bacteria drive autoimmune arthritis via T helper 17 cells
- PMID: 20620945
- PMCID: PMC2904693
- DOI: 10.1016/j.immuni.2010.06.001
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.
Copyright 2010 Elsevier Inc. All rights reserved.
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Comment in
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Commensal flora: friends or foes?Immunotherapy. 2011 Mar;3(3):313-4. doi: 10.2217/imt.11.1. Immunotherapy. 2011. PMID: 21395373 No abstract available.
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