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Critical roles for Rac GTPases in T-cell migration to and within lymph nodes.

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Publication date 2010
Author Faroudi Mustapha, Hons Miroslav, Zachacz Agnieszka, Dumont Celine, Lyck Ruth, Stein Jens V, Tybulewicz Victor L J,
Project Examining the function of lymphoid organ structure during antiviral immune responses using microscopic and mesoscopic imaging
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Original article (peer-reviewed)

Journal Blood
Volume (Issue) 116(25)
Page(s) 5536 - 47
Title of proceedings Blood
DOI 10.1182/blood-2010-08-299438

Abstract

Naive T cells continuously recirculate between secondary lymphoid tissue via the blood and lymphatic systems, a process that maximizes the chances of an encounter between a T cell and its cognate antigen. This recirculation depends on signals from chemokine receptors, integrins, and the sphingosine-1-phosphate receptor. The authors of previous studies in other cell types have shown that Rac GTPases transduce signals leading to cell migration and adhesion; however, their roles in T cells are unknown. By using both 3-dimensional intravital and in vitro approaches, we show that Rac1- and Rac2-deficient T cells have multiple defects in this recirculation process. Rac-deficient T cells home very inefficiently to lymph nodes and the white pulp of the spleen, show reduced interstitial migration within lymph node parenchyma, and are defective in egress from lymph nodes. These mutant T cells show defective chemokine-induced chemotaxis, chemokinesis, and adhesion to integrin ligands. They have reduced lateral motility on endothelial cells and transmigrate in-efficiently. These multiple defects stem from critical roles for Rac1 and Rac2 in transducing chemokine and sphingosine-1-phosphate receptor 1 signals leading to motility and adhesion.
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