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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    • "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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    ILAR journal / National Research Council, Institute of Laboratory Animal Resources 08/2015; 56(2). DOI:10.1093/ilar/ilv021 · 2.39 Impact Factor
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    • "For instance, a recent experimental study using an osteomyelitis mice model has shown that diet can modulate the microbiome (high fat diet induces a decrease in Prevotella), which in turn offered protection against inflammatory bone disease (Lukens et al., 2014). Increasing evidence suggests that alteration of the microbiota not only has effects on intestinal conditions such as Crohn's and other Inflammatory Bowel Diseases (Gevers et al., 2014; Morgan et al., 2012), but also in the development of systemic immune diseases such as rheumatoid arthritis (Scher & Abramson, 2011; Wu et al., 2010), type I diabetes (Kriegel et al., 2011; Suez et al., 2014), and allergic diseases (Castro-Nallar et al., in press; Hong et al., 2010; Nakayama et al., 2011; Pérez-Losada et al., 2015). "
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    PeerJ 08/2015; 3(8):e1140. DOI:10.7717/peerj.1140 · 2.11 Impact Factor
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    • "A number of microorganisms, including Klebsiella pneumoniae, Proteus mirabilis , and segmented filamentous bacteria (SFB), have been implicated as necessary, and in some cases sufficient (Garrett et al., 2010; Wu et al., 2010). However, although it is well established that IL-17-producing T cells are activated by microbial components in the gut environment (Ivanov et al., 2009; Wu et al., 2010), it is unclear how this relates to activation of tissuespecific autoimmune T cells. The recently published evidence that the Th17 cells elicited by SFB are actually specific to SFB antigens (Goto et al., 2014; Yang et al., 2014) makes the connection to tissue-specific pathology even less clear. "
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    Immunity 08/2015; 43(2):343-53. DOI:10.1016/j.immuni.2015.07.014 · 21.56 Impact Factor
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