Figure 2. An autoimmune arthritis model that demonstrates the link between gut microbiota and an extraintestinal disease. The K/BxN arthritis model was used to demonstrate how the gut microbiota can influence a non-gut-associated disease. K/BxN mice express a transgene-encoded T-cell receptor that reacts to a self-peptide. Colonization of SFB on the gut induces the differentiation of Th17 cells (step 1 and 2), which subsequently exit the gut and migrate into the peripheral lymphoid tissue. The gut-origin of Th17 cells can be identified by their expression of the α4β7 receptor, imprinted on these T cells by intestinal-mucosa-associated DCs (step 3). IL-17, in turn, acts directly on B cells to provide help in the differentiation of germinal center B cells and the production of autoantibody in spleen (step 4). The autoantibody then circulates into its target organ joints, which ultimately leads to the development of disease.