Expression of αvβ8 integrin on dendritic cells regulates Th17 cell development and experimental autoimmune encephalomyelitis in mice
Andrew C. Melton, … , Jeffrey A. Bluestone, Dean Sheppard
Andrew C. Melton, … , Jeffrey A. Bluestone, Dean Sheppard
Published November 22, 2010
Citation Information: J Clin Invest. 2010;120(12):4436-4444. https://doi.org/10.1172/JCI43786.
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Research Article

Expression of αvβ8 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-β is required for conversion of naive T cells to Th17 cells, but the mechanisms regulating this process are unknown. Integrin αvβ8 on DCs can activate TGF-β, and this process contributes to the development of induced Tregs. Here, we have now shown that integrin αvβ8 expression on DCs plays a critical role in the differentiation of Th17 cells. Th17 cells were nearly absent in the colons of mice lacking αvβ8 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 αvβ8 on DCs showed near-complete protection from experimental autoimmune encephalomyelitis. Our results therefore suggest that the integrin αvβ8 pathway is biologically important and that αvβ8 expression on DCs could be a therapeutic target for the treatment of Th17-driven autoimmune disease.

Authors

Andrew C. Melton, Samantha L. Bailey-Bucktrout, Mark A. Travis, Brian T. Fife, Jeffrey A. Bluestone, Dean Sheppard

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Figure 2

β8fl/fl × CD11c-cre mice are protected from EAE.

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β8fl/fl × CD11c-cre mice are protected from EAE. (A) Clinical scores...
(A) Clinical scores of control and β8fl/fl × CD11c-cre mice after EAE immunization. (B) Total number of CD4 and CD8 T cells isolated from the CNS of control or β8fl/fl × CD11c-cre mice on day 19 after EAE immunization. (C) Flow cytometry plots of CD4+ T cells from the CNS of control or β8fl/fl × CD11c-cre mice on day 19 after EAE immunization. Cells were activated with PMA/ionomycin and then stained for IL-17 and IFN-γ. (D) Percentage of IL-17– and IFN-γ–producing CD4+ T cells from the CNS of control and β8fl/fl × CD11c-cre mice. (E) Flow cytometry plots of CD4+ T cells from the draining lymph nodes of control or β8fl/fl × CD11c-cre mice on day 8 after EAE immunization. Cells were activated with PMA/ionomycin and then stained for IL-17 and IFN-γ. (F) Percentage of IL-17– and IFN-γ–producing CD4+ T cells from the draining lymph nodes of control and β8fl/fl × CD11c-cre mice. Data represent the means ± SEM of 3 independent experiments and at least 10 mice in each group. *P < 0.01.