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      Integral Roles for Integrins in γδ T Cell Function

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          Abstract

          Integrins are adhesion receptors on the cell surface that enable cells to respond to their environment. Most integrins are heterodimers, comprising α and β type I transmembrane glycoprotein chains with large extracellular domains and short cytoplasmic tails. Integrins deliver signals through multiprotein complexes at the cell surface, which interact with cytoskeletal and signaling proteins to influence gene expression, cell proliferation, morphology, and migration. Integrin expression on γδ T cells (γδTc) has not been systematically investigated; however, reports in the literature dating back to the early 1990s reveal an understated role for integrins in γδTc function. Over the years, integrins have been investigated on resting and/or activated peripheral blood-derived polyclonal γδTc, γδTc clones, as well as γδ T intraepithelial lymphocytes. Differences in integrin expression have been found between αβ T cells (αβTc) and γδTc, as well as between Vδ1 and Vδ2 γδTc. While most studies have focused on human γδTc, research has also been carried out in mouse and bovine models. Roles attributed to γδTc integrins include adhesion, signaling, activation, migration, tissue localization, tissue retention, cell spreading, cytokine secretion, tumor infiltration, and involvement in tumor cell killing. This review attempts to encompass all reports of integrins expressed on γδTc published prior to December 2017, highlights areas warranting further investigation, and discusses the relevance of integrin expression for γδTc function.

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          Most cited references74

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          Arg-Gly-Asp: a versatile cell recognition signal.

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            Chemokines and the arrest of lymphocytes rolling under flow conditions.

            Circulating lymphocytes are recruited from the blood to the tissue by rolling along the endothelium until being stopped by a signaling event linked to the Gialpha subunit of a heterotrimeric GTP-binding protein; that event then triggers rapid integrin-dependent adhesion. Four chemokines are now shown to induce such adhesion to intercellular adhesion molecule-1 and to induce arrest of rolling cells within 1 second under flow conditions similar to those of blood. SDF-1 (also called PBSF), 6-C-kine (also called Exodus-2), and MIP-3beta (also called ELC or Exodus-3) induced adhesion of most circulating lymphocytes, including most CD4+ T cells; and MIP-3alpha (also called LARC or Exodus-1) triggered adhesion of memory, but not naïve, CD4+ T cells. Thus, chemokines can regulate the arrest of lymphocyte subsets under flowing conditions, which may allow them to control lymphocyte-endothelial cell recognition and lymphocyte recruitment in vivo.
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              VLA proteins in the integrin family: structures, functions, and their role on leukocytes.

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                Author and article information

                Contributors
                URI : http://frontiersin.org/people/u/165642
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                13 March 2018
                2018
                : 9
                : 521
                Affiliations
                [1] 1Experimental Oncology, University of Alberta , Edmonton, AB, Canada
                Author notes

                Edited by: Pierre Vantourout, King’s College London, United Kingdom

                Reviewed by: Vicky Morrison, University of Glasgow, United Kingdom; Wendy L. Havran, The Scripps Research Institute, United States; C. David Pauza, American Gene Technologies International Inc., United States

                *Correspondence: Gabrielle M. Siegers, siegers@ 123456ualberta.ca

                Specialty section: This article was submitted to T Cell Biology, a section of the journal Frontiers in Immunology

                Article
                10.3389/fimmu.2018.00521
                5859029
                29593745
                8d1c466f-45bd-4ee6-80f4-310f33205b71
                Copyright © 2018 Siegers.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 15 January 2018
                : 28 February 2018
                Page count
                Figures: 1, Tables: 1, Equations: 0, References: 82, Pages: 8, Words: 6710
                Funding
                Funded by: Cancer Research Society 10.13039/100009326
                Award ID: CRSOG2013
                Categories
                Immunology
                Mini Review

                Immunology
                gamma delta t cells,adhesion and signaling molecules,cellular migration,tissue retention,tissue localization,tumor infiltrating lymphocytes,cytotoxicity,cytokine secretion

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