Expression of ?v?8 integrin on dendritic cells regulates Th17 cell development and experimental autoimmune encephalomyelitis in mice.

ABSTRACT: Th17 cells promote a variety of autoimmune diseases, including psoriasis, multiple sclerosis, rheumatoid arthritis, and inflammatory bowel disease. TGF-? is required for conversion of naive T cells to Th17 cells, but the mechanisms regulating this process are unknown. Integrin ?v?8 on DCs can activate TGF-?, and this process contributes to the development of induced Tregs. Here, we have now shown that integrin ?v?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 ?v?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 ?v?8 on DCs showed near-complete protection from experimental autoimmune encephalomyelitis. Our results therefore suggest that the integrin ?v?8 pathway is biologically important and that ?v?8 expression on DCs could be a therapeutic target for the treatment of Th17-driven autoimmune disease.

SUBMITTER: Melton AC 

PROVIDER: S-EPMC2993595 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature