The gut microbiota regulates K/BxN autoimmune arthritis independent of Th17 and IL-17 (BA6P.121)

Abstract

Abstract The bacterial community that colonizes mucosal surfaces helps shape the development and function of the immune system. The effect of the microbiota on autoimmunity has important implications, although the mechanisms are not well understood. The K/BxN mouse model of rheumatoid arthritis is dependent on the microbiota, and particularly on segmented filamentous bacteria (SFB), for the autoimmune phenotype. Because SFB potently induce Th17 cell differentiation, previous studies have suggested Th17 cells as the link between microbiota and arthritis. In this study we sought to test directly the functional significance of Th17 and IL-17 in arthritis development by genetic approaches. We utilized mice deficient for either transcription factor RORγt (which controls the Th17 program), or the cytokine IL-17A (the major cytokine of the IL-17 family) in both cell transfer and spontaneous disease models. Unexpectedly, mice without Th17 or IL-17 were not protected from disease. Germinal center B and follicular helper T cell (Tfh) populations were normal, as were levels of serum IgG against self antigen. We found no evidence for compensation in production of the related cytokine IL-17F in IL-17A deficient mice. However, antibiotic treatment prevented disease in both IL-17 deficient and sufficient K/BxN mice, and resulted in defective Tfh and germinal center B cell differentiation. We conclude that the gut microbiota promotes autoimmune development by mechanisms independent of Th17 or IL-17.