Integrin Activation Controls Regulatory T Cell-Mediated Peripheral Tolerance
Autor: | Jailal N. G. Ablack, Mark H. Ginsberg, Jack D. Bui, Kelly A. Remedios, John T. Chang, Patrick J. Metz, Li-Fan Lu, Joseph M. Cantor, Jane E. Klann, Zhaoren He, Jocelyn G. Olvera, Stephanie H. Kim, Justine Lopez, Brian G. Petrich, Tiffani Tysl, Gene W. Yeo, Ye Zheng, Brigid S. Boland |
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Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Talin Integrins Regulatory T cell Immunology Cell Mutant Integrin chemical and pharmacologic phenomena Autoimmunity medicine.disease_cause T-Lymphocytes Regulatory Article Transcriptome 03 medical and health sciences Mice 0302 clinical medicine medicine Immunology and Allergy Animals Inflammation biology Chemistry Peripheral Tolerance Peripheral tolerance hemic and immune systems Transmembrane protein Cell biology 030104 developmental biology medicine.anatomical_structure biology.protein 030215 immunology |
Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 200(12) |
ISSN: | 1550-6606 |
Popis: | Maintenance of the regulatory T (Treg) cell pool is essential for peripheral tolerance and prevention of autoimmunity. Integrins, heterodimeric transmembrane proteins consisting of α and β subunits that mediate cell-to-cell and cell-to-extracellular matrix interactions, play an important role in facilitating Treg cell contact–mediated suppression. In this article, we show that integrin activation plays an essential, previously unappreciated role in maintaining murine Treg cell function. Treg cell–specific loss of talin, a β integrin–binding protein, or expression of talin(L325R), a mutant that selectively abrogates integrin activation, resulted in lethal systemic autoimmunity. This dysfunction could be attributed, in part, to a global dysregulation of the Treg cell transcriptome. Activation of integrin α4β1 led to increased suppressive capacity of the Treg cell pool, suggesting that modulating integrin activation on Treg cells may be a useful therapeutic strategy for autoimmune and inflammatory disorders. Taken together, these results reveal a critical role for integrin-mediated signals in controlling peripheral tolerance by virtue of maintaining Treg cell function. |
Databáze: | OpenAIRE |
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