Expression of αvβ8 integrin on dendritic cells regulates Th17 cell development and experimental autoimmune encephalomyelitis in mice

Th17 cells promote a variety of autoimmune diseases, including psoriasis, multiple sclerosis, rheumatoid arthritis, and inflammatory bowel disease. TGF-beta is required for conversion of naive T cells to Th17 cells, but the mechanisms regulating this process are unknown. Integrin alpha v beta 8 on DCs can activate TGF-beta, and this process contributes to the development of induced Tregs. Here, we have now shown that integrin alpha v beta 8 expression on DCs plays a critical role in the differentiation of Th17 cells. Th17 cells were nearly absent in the colons of mice lacking alpha v beta 8 expression on DCs. In addition, these mice and the DCs harvested from them had an impaired ability to convert naive T cells into Th17 cells in vivo and in vitro, respectively. Importantly, mice lacking alpha v beta 8 on DCs showed near-complete protection from experimental autoimmune encephalomyelitis. Our results therefore suggest that the integrin alpha v beta 8 pathway is biologically important and that alpha v beta 8 expression on DCs could be a therapeutic target for the treatment of Th17-driven autoimmune disease.