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. |