In:
The Journal of Immunology, The American Association of Immunologists, Vol. 196, No. 1_Supplement ( 2016-05-01), p. 125.3-125.3
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-cell and cell-extracellular matrix interactions, have been shown to play an important role in facilitating cell contact-mediated suppression by Treg cells. Here we show that integrin activation plays an essential, previously unappreciated role in maintaining the stability of the Treg cell pool. Treg cell-specific loss of talin1, a β integrin-binding protein, or expression of talin1(L325R), a mutant that selectively abrogates integrin activation, resulted in dysregulation of Treg cell identity and lethal systemic autoimmunity. Moreover, the absence of sustained interactions between the integrin LFA-1 on Treg cells and its ligand ICAM-1 on dendritic cells reduced the expression of Foxp3 and caused Treg cells to adopt an effector CD4+ T cell-like phenotype. Taken together, these results reveal a critical role for tonic, integrin-mediated signals in controlling peripheral tolerance by virtue of maintaining Treg cell identity and stability.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.196.Supp.125.3
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2016
detail.hit.zdb_id:
1475085-5
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