LFA-1 in T cell priming, differentiation, and effector functions

TY - JOUR

T1 - LFA-1 in T cell priming, differentiation, and effector functions

AU - Gérard, Audrey

AU - Cope, Andrew P.

AU - Kemper, Claudia

AU - Alon, Ronen

AU - Köchl, Robert

N1 - Funding Information: The research described in this review was supported by: the Kennedy Trust for Rheumatology Research ( KENN151607 ), the BBSRC ( BB/R015651/1 ), and Cancer Research UK ( C65275/A29549 ) (to A.G); Arthritis Research UK grants 19652 and 20525 , a Royal Society collaborative travel grant , and a Wellcome Trust project grant 086054 (to A.P.C.); the Israel Science Foundation (grant no. 791/17 ), the Minerva Foundation , ERA-Net E-Rare-3 , and GIF (grant number I-1470-412.13/2018 ) (to R.A.); the Division of Intramural Research of the National Heart, Lung, and Blood Institute , NIH (to C.K.); and the Academy of Medical Sciences Springboard award ( SBF006\1100 ) (to R.K.). Publisher Copyright: © 2021 Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/8

Y1 - 2021/8

N2 - The integrin LFA-1 is crucial for T cell entry into mammalian lymph nodes and tissues, and for promoting interactions with antigen-presenting cells (APCs). However, it is increasingly evident that LFA-1 has additional key roles beyond the mere support of adhesion between T cells, the endothelium, and/or APCs. These include roles in homotypic T cell–T cell (T–T) communication, the induction of intracellular complement activity underlying Th1 effector cell polarization, and the support of long-lasting T cell memory. Here, we briefly summarize current knowledge of LFA-1 biology, discuss novel cytoskeletal regulators of LFA-1 functions, and review new aspects of LFA-1 mechanobiology that are relevant to its function in immunological synapses and in specific pathologies arising from LFA-1 dysregulation.

AB - The integrin LFA-1 is crucial for T cell entry into mammalian lymph nodes and tissues, and for promoting interactions with antigen-presenting cells (APCs). However, it is increasingly evident that LFA-1 has additional key roles beyond the mere support of adhesion between T cells, the endothelium, and/or APCs. These include roles in homotypic T cell–T cell (T–T) communication, the induction of intracellular complement activity underlying Th1 effector cell polarization, and the support of long-lasting T cell memory. Here, we briefly summarize current knowledge of LFA-1 biology, discuss novel cytoskeletal regulators of LFA-1 functions, and review new aspects of LFA-1 mechanobiology that are relevant to its function in immunological synapses and in specific pathologies arising from LFA-1 dysregulation.

KW - adhesion

KW - complement

KW - LFA-1

KW - mechanosensing

KW - mechanotransduction

KW - PTPN22

KW - WNK1

UR - https://www.scopus.com/pages/publications/85111020033

U2 - 10.1016/j.it.2021.06.004

DO - 10.1016/j.it.2021.06.004

M3 - Review article

AN - SCOPUS:85111020033

SN - 1471-4906

VL - 42

SP - 706

EP - 722

JO - TRENDS IN IMMUNOLOGY

JF - TRENDS IN IMMUNOLOGY

IS - 8

ER -