Expression of αvß8 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-ß is required for conversion of naive T cells to Th17 cells, but the mechanisms regulating this process are unknown. Integrin αvß8 on DCs can activate TGF-ß, and this process contributes to the development of induced Tregs. Here, we have now shown that integrin αvß8 expression on DCs plays a critical role in the differentiation of Th17 cells. Th17 cells were nearly absent in the colons of mice lacking αvß8 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 αvß8 on DCs showed near-complete protection from experimental autoimmune encephalomyelitis. Our results therefore suggest that the integrin αvß8 pathway is biologically important and that αvß8 expression on DCs could be a therapeutic target for the treatment of Th17-driven autoimmune disease.