Integrin Activation Controls Regulatory T Cell-Mediated Peripheral Tolerance

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 fac...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of immunology (1950) 2018-06, Vol.200 (12), p.4012-4023
Main Authors: Klann, Jane E, Kim, Stephanie H, Remedios, Kelly A, He, Zhaoren, Metz, Patrick J, Lopez, Justine, Tysl, Tiffani, Olvera, Jocelyn G, Ablack, Jailal N, Cantor, Joseph M, Boland, Brigid S, Yeo, Gene, Zheng, Ye, Lu, Li-Fan, Bui, Jack D, Ginsberg, Mark H, Petrich, Brian G, Chang, John T
Format: Article
Language:English
Subjects:
Autoimmunity
Cell activation
Cell adhesion & migration
Extracellular matrix
Gene expression
Immunological tolerance
Inflammatory diseases
Integrins
Lymphocytes T
Membrane proteins
Proteins
Talin
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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 α β 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.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.1800112