Expression of [alpha]v[Beta]8 integrin on dendritic cells regulates Th17 cell development and experimental autoimmune encephalomyelitis in mice

• Published in: The Journal of clinical investigation 2010-12, Vol.120 (12), p.4436
• Main Authors: Melton, Andrew C, Bailey-Bucktrout, Samantha L, Travis, Mark A, Fife, Brian T, Bluestone, Jeffrey A, Sheppard, Dean
• Format: Article
• Language: English
• Subjects: Biomedical research
• ISSN: 0021-9738; 1558-8238

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 αv[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 αv[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 αv[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 αv[beta]8 on DCs showed near-complete protection from experimental autoimmune encephalomyelitis. Our results therefore suggest that the integrin αv[beta]8 pathway is biologically important and that αv[beta]8 expression on DCs could be a therapeutic target for the treatment of Th17-driven autoimmune disease.