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J Immunol. 2017 Jun 15;198(12):4639-4651. doi: 10.4049/jimmunol.1601165. Epub 2017 May 17.

Talin Plays a Critical Role in the Maintenance of the Regulatory T Cell Pool.

Author information

1
Department of Medicine, University of California San Diego, La Jolla, CA 92093.
2
Nomis Foundation Laboratories for Immunobiology and Microbial Pathogenesis, Salk Institute for Biological Studies, La Jolla, CA 92037; and.
3
Department of Pediatrics, Aflac Cancer and Blood Disorders Center, Emory University School of Medicine, Atlanta, GA 30322 changj@ucsd.edu brian.petrich@emory.edu.
4
Department of Medicine, University of California San Diego, La Jolla, CA 92093; changj@ucsd.edu brian.petrich@emory.edu.

Abstract

Talin, a cytoskeletal protein essential in mediating integrin activation, has been previously shown to be involved in the regulation of T cell proliferation and function. In this study, we describe a role for talin in maintaining the homeostasis and survival of the regulatory T (Treg) cell pool. T cell-specific deletion of talin in Tln1fl/flCd4Cre mice resulted in spontaneous lymphocyte activation, primarily due to numerical and functional deficiencies of Treg cells in the periphery. Peripheral talin-deficient Treg cells were unable to maintain high expression of IL-2Rα, resulting in impaired IL-2 signaling and ultimately leading to increased apoptosis through downregulation of prosurvival proteins Bcl-2 and Mcl-1. The requirement for talin in maintaining high IL-2Rα expression by Treg cells was due, in part, to integrin LFA-1-mediated interactions between Treg cells and dendritic cells. Collectively, our data suggest a critical role for talin in Treg cell-mediated maintenance of immune homeostasis.

PMID:
28515282
PMCID:
PMC5507362
DOI:
10.4049/jimmunol.1601165
[Indexed for MEDLINE]
Free PMC Article

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