在免疫响应的有益激发与免疫系统对正常组织的不适当攻击之间保持平衡，需要多种抑制和平衡作用。Cytokine TGFβ (transforming growth factor-β)在这样一种通道中是一个主要因子，充当适应性免疫的一个负调控因子，但一直不清楚是什么激发TGFβ的，也不清楚哪些免疫细胞是其作用的关键。现在，Integrin αvβ8被发现是TGFβ的一个关键激发因子；组织树状细胞上这种Integrin的失去会激发TGFβ，后者又会诱导调控性T-细胞。在缺少这种通道时，小鼠会出现自免疫，其结肠会发生严重炎症，类似于人类的溃疡性结肠炎。
原始出处：
Nature 449, 361-365 (20 September 2007) | doi:10.1038/nature06110; Received 9 April 2007; Accepted 23 July 2007; Published online 12 August 2007
Loss of integrin v8 on dendritic cells causes autoimmunity and colitis in mice
Mark A. Travis1,5, Boris Reizis2, Andrew C. Melton1, Emma Masteller3, Qizhi Tang3, John M. Proctor4, Yanli Wang1, Xin Bernstein1, Xiaozhu Huang1, Louis F. Reichardt4, Jeffrey A. Bluestone3 & Dean Sheppard1
Lung Biology Center, Department of Medicine, University of California San Francisco, 1550 4th Street, Room 545, San Francisco, California 94158, USA
Department of Microbiology, Columbia University, 701 West 168th Street, Room 609, New York, New York 10032, USA
Diabetes Center, Department of Medicine, 513 Parnassus Avenue, University of San Francisco, San Francisco, California 94143, USA
Howard Hughes Medical Institute, Department of Physiology, University of California, San Francisco, California 94158, USA
Present address: Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, A3051 Smith Building, Oxford Road, Manchester M13 9PT, UK.
Correspondence to: Dean Sheppard1 Correspondence and requests for materials should be addressed to D.S. (Email: dean.sheppard@ucsf.edu).
The cytokine transforming growth factor- (TGF-) is an important negative regulator of adaptive immunity1, 2, 3. TGF- is secreted by cells as an inactive precursor that must be activated to exert biological effects4, but the mechanisms that regulate TGF- activation and function in the immune system are poorly understood. Here we show that conditional loss of the TGF--activating integrin v8 on leukocytes causes severe inflammatory bowel disease and age-related autoimmunity in mice. This autoimmune phenotype is largely due to lack of v8 on dendritic cells, as mice lacking v8 principally on dendritic cells develop identical immunological abnormalities as mice lacking v8 on all leukocytes, whereas mice lacking v8 on T cells alone are phenotypically normal. We further show that dendritic cells lacking v8 fail to induce regulatory T cells (TR cells) in vitro, an effect that depends on TGF- activity. Furthermore, mice lacking v8 on dendritic cells have reduced proportions of TR cells in colonic tissue. These results suggest that v8-mediated TGF- 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 v8 on dendritic cells to induce and/or maintain tissue TR cells.
