Gut-Residing Segmented Filamentous Bacteria Drive Autoimmune Arthritis via T Helper 17 Cells

Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
Immunity (Impact Factor: 21.56). 06/2010; 32(6):815-27. DOI: 10.1016/j.immuni.2010.06.001
Source: PubMed


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.

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    • "RA has recently been associated with changes in the gut microbiota (Scher et al., 2013;Zhang et al., 2015). In spontaneous mouse models of autoimmune arthritis, joint inflammation is attenuated under germ-free conditions, but colonisation of the gut with commensal microbes is sufficient to elicit joint inflammation comparable to that observed in conventional mice (Abdollahi-Roodsaz et al., 2008;Wu et al., 2010). In these models, the colonisation of the gut resulted in a perturbed Treg/Teff balance, which was associated with disease onset and progression. "
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    • "This induction of Th17 cells was important in protection against oral infection with Citrobacter rodentium (Ivanov et al., 2009). Furthermore, SFB has been shown to drive pathology in mouse models of rheumatoid arthritis and multiple sclerosis via the induction of inflammatory Th17 cells, demonstrating that this bacterium can act as a pathobiont in the context of host autoimmunity (Wu et al., 2010). "
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    • "While there are undoubtedly exceptions, mice from The Jackson Laboratory are largely free of SFB, while most mice from other commercial sources are endemically colonized. SFB has a well-recognized influence on the ontogeny of the mucosal immune system and has been shown to significantly affect several mouse models of both enteric and systemic disease (Denning et al. 2011; Ivanov et al. 2009; Lee et al. 2011; Wu et al. 2010). For a more detailed description of the physiological effects of SFB, readers are referred to a recent review on the topic (Ericsson, Hagan et al. 2014). "
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