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Publication : The Rac activator Tiam1 controls efficient T-cell trafficking and route of transendothelial migration.

First Author  Gérard A Year  2009
Journal  Blood Volume  113
Issue  24 Pages  6138-47
PubMed ID  19139083 Mgi Jnum  J:149331
Mgi Id  MGI:3848308 Doi  10.1182/blood-2008-07-167668
Citation  Gerard A, et al. (2009) The Rac activator Tiam1 controls efficient T-cell trafficking and route of transendothelial migration. Blood 113(24):6138-47
abstractText  Migration toward chemoattractants is a hallmark of T-cell trafficking and is essential to produce an efficient immune response. Here, we have analyzed the function of the Rac activator Tiam1 in the control of T-cell trafficking and transendothelial migration. We found that Tiam1 is required for chemokine- and S1P-induced Rac activation and subsequent cell migration. As a result, Tiam1-deficient T cells show reduced chemotaxis in vitro, and impaired homing, egress, and contact hypersensitivity in vivo. Analysis of the T-cell transendothelial migration cascade revealed that PKCzeta/Tiam1/Rac signaling is dispensable for T-cell arrest but is essential for the stabilization of polarization and efficient crawling of T cells on endothelial cells. T cells that lack Tiam1 predominantly transmigrate through individual endothelial cells (transcellular migration) rather than at endothelial junctions (paracellular migration), suggesting that T cells are able to change their route of transendothelial migration according to their polarization status and crawling capacity.
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