Loss of integrin αvβ8 on dendritic cells causes autoimmunity and colitis in mice

Mark A. Travis, Boris Reizis, Andrew C. Melton, Emma Masteller, Qizhi Tang, John M. Proctor, Yanli Wang, Xin Bernstein, Xiaozhu Huang, Louis F. Reichardt, Jeffrey A. Bluestone, Dean Sheppard

    Research output: Contribution to journalArticlepeer-review


    The cytokine transforming growth factor-β (TGF-β) is an important negative regulator of adaptive immunity. TGF-β is secreted by cells as an inactive precursor that must be activated to exert biological effects, but the mechanisms that regulate TGF-β activation and function in the immune system are poorly understood. Here we show that conditional loss of the TGF-β-activating integrin αvβ8 on leukocytes causes severe inflammatory bowel disease and age-related autoimmunity in mice. This autoimmune phenotype is largely due to lack of αvβ8 on dendritic cells, as mice lacking αvβ8 principally on dendritic cells develop identical immunological abnormalities as mice lacking αvβ 8 on all leukocytes, whereas mice lacking αvβ 8 on T cells alone are phenotypically normal. We further show that dendritic cells lacking αvβ8 fail to induce regulatory T cells (TR cells) in vitro, an effect that depends on TGF-β activity. Furthermore, mice lacking αvβ 8 on dendritic cells have reduced proportions of TR cells in colonic tissue. These results suggest that αvβ 8-mediated TGF-β activation by dendritic cells is essential for preventing immune dysfunction that results in inflammatory bowel disease and autoimmunity, effects that are due, at least in part, to the ability of αvβ8 on dendritic cells to induce and/or maintain tissue TR cells. ©2007 Nature Publishing Group.
    Original languageEnglish
    Pages (from-to)361-365
    Number of pages4
    Issue number7160
    Publication statusPublished - 20 Sept 2007


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