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 and Dean Sheppard ()
Additional contact information
Mark A. Travis: Lung Biology Center, University of California San Francisco, 1550 4th Street, Room 545, San Francisco, California 94158, USA
Boris Reizis: Columbia University, 701 West 168th Street, Room 609, New York, New York 10032, USA
Andrew C. Melton: Lung Biology Center, University of California San Francisco, 1550 4th Street, Room 545, San Francisco, California 94158, USA
Emma Masteller: Diabetes Center, 513 Parnassus Avenue, University of San Francisco, San Francisco, California 94143, USA
Qizhi Tang: Diabetes Center, 513 Parnassus Avenue, University of San Francisco, San Francisco, California 94143, USA
John M. Proctor: Howard Hughes Medical Institute, University of California, San Francisco, California 94158, USA
Yanli Wang: Lung Biology Center, University of California San Francisco, 1550 4th Street, Room 545, San Francisco, California 94158, USA
Xin Bernstein: Lung Biology Center, University of California San Francisco, 1550 4th Street, Room 545, San Francisco, California 94158, USA
Xiaozhu Huang: Lung Biology Center, University of California San Francisco, 1550 4th Street, Room 545, San Francisco, California 94158, USA
Louis F. Reichardt: Howard Hughes Medical Institute, University of California, San Francisco, California 94158, USA
Jeffrey A. Bluestone: Diabetes Center, 513 Parnassus Avenue, University of San Francisco, San Francisco, California 94143, USA
Dean Sheppard: Lung Biology Center, University of California San Francisco, 1550 4th Street, Room 545, San Francisco, California 94158, USA

Nature, 2007, vol. 449, issue 7160, 361-365

Abstract: Balancing the immune forces Maintaining a balance between beneficial activation of immune responses and inappropriate immune attack of normal tissues requires multiple checks and balances. The cytokine TGF-β (transforming growth factor-β) is major player in one such pathway, as a negative regulator of adaptive immunity, but it has been unclear what activates TGF-β and which immune cells are critical to its action. Now the integrin αvβ8 has been identified as a critical activator of TGF-β; loss of this integrin on tissue dendritic cells activates TGF-β, which in turn induces regulatory T cells. In the absence of this pathway, mice develop autoimmunity and severe inflammation of the colon that resembles human ulcerative colitis.

Date: 2007
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DOI: 10.1038/nature06110

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