The Rac activator Tiam1 controls efficient T-cell trafficking and route of transendothelial migration
The Rac activator Tiam1 controls efficient T-cell trafficking and route of transendothelial migration
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DOI：
10.1182/blood-2008-07-167668
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发表时间：
2009-06-11
期刊：
影响因子：
20.3
通讯作者：
Collard, John G.
中科院分区：
文献类型：
--
作者：
Gerard, Audrey;van der Kammen, Rob A.;Collard, John G.
向化学引诱物的迁移是T细胞运输的标志，对于产生有效的免疫应答至关重要。在这里，我们分析了Rac激活剂Tiam 1在控制T细胞运输和跨内皮迁移中的功能。我们发现Tiam 1是趋化因子和S1 P诱导的Rac激活和随后的细胞迁移所必需的。因此，Tiam 1缺陷型T细胞在体外表现出趋化性降低，在体内表现出归巢、外出和接触超敏反应受损。对T细胞跨内皮迁移级联反应的分析表明，PKC zeta/Tiam 1/Rac信号传导对于T细胞停滞是不可或缺的，但对于T细胞在内皮细胞上的极化和有效爬行的稳定是必不可少的。缺乏Tiam 1的T细胞主要通过单个内皮细胞（跨细胞迁移）而不是在内皮连接处（细胞旁迁移）迁移，这表明T细胞能够根据其极化状态和爬行能力改变其跨内皮迁移的途径。（血。2009; 113：6138-6147）
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 PKC zeta/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. ( Blood. 2009; 113: 6138-6147)