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

Faroudi, Mustapha; Hons, Miroslav; Zachacz, Agnieszka; Dumont, Celine; Lyck, Ruth; Stein, Jens V; Tybulewicz, Victor L J (2010). Critical roles for Rac GTPases in T-cell migration to and within lymph nodes. Blood, 116(25), pp. 5536-47. Washington, D.C.: American Society of Hematology 10.1182/blood-2010-08-299438

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute

UniBE Contributor:

Hons, Miroslav; Lyck, Ruth and Stein, Jens Volker

ISSN:

0006-4971

Publisher:

American Society of Hematology

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:11

Last Modified:

04 May 2014 23:05

Publisher DOI:

10.1182/blood-2010-08-299438

PubMed ID:

20870900

Web of Science ID:

000285383900017

URI:

https://boris.unibe.ch/id/eprint/2161 (FactScience: 204417)

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