Format

Send to

Choose Destination
J Immunol. 2018 Jun 15;200(12):4012-4023. doi: 10.4049/jimmunol.1800112. Epub 2018 Apr 27.

Integrin Activation Controls Regulatory T Cell-Mediated Peripheral Tolerance.

Author information

1
Department of Medicine, University of California, San Diego, La Jolla, CA 92093.
2
Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093.
3
Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA 92093.
4
Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore.
5
Nomis Foundation Laboratories for Immunobiology and Microbial Pathogenesis, Salk Institute for Biological Studies, La Jolla, CA 92037.
6
Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093.
7
Department of Pathology, University of California, San Diego, La Jolla, CA 92093; and.
8
Aflac Cancer and Blood Disorders Center, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322 changj@ucsd.edu brian.petrich@emory.edu.
9
Department of Medicine, University of California, San Diego, La Jolla, CA 92093; changj@ucsd.edu brian.petrich@emory.edu.

Abstract

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.

PMID:
29703862
PMCID:
PMC5988969
DOI:
10.4049/jimmunol.1800112
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center