SLP-76 is required for optimal CXCR4-stimulated T lymphocyte firm arrest to ICAM-1 under shear flow.
SLP-76 is required for optimal CXCR4-stimulated T lymphocyte firm arrest to ICAM-1 under shear flow.
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DOI：
10.1002/eji.201142303
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发表时间：
2012-10
影响因子：
5.4
通讯作者：
Hammer, Daniel A.
中科院分区：
文献类型：
--
作者：
Lee, Dooyoung;Kim, Jiyeon;Baker, Rebecca G.;Koretzky, Gary A.;Hammer, Daniel A.
在趋化因子受体参与后，T细胞在靶位点的快速停滞对免疫系统的正常功能至关重要。虽然T细胞停滞总是发生在体内的流体动力学的力量，大多数研究的分子机制的逮捕已在静态条件下进行。虽然衔接蛋白SLP-76在TCR诱导的整联蛋白活化中的需求已被证明，但其在趋化因子触发的T细胞粘附中的作用尚不清楚。使用流动室系统，我们表明SLP-76在调节响应CXCL 12 α SDF-1α的生理剪切流下T细胞从束缚和滚动到牢固粘附的转变中起重要作用; SLP-76缺陷的原代T细胞表现出粘附缺陷，牢固停滞的细胞数量显著减少。我们进一步证明了SLP-76的N-末端磷酸酪氨酸在流动下的T细胞粘附中起着关键作用。这些发现揭示了SLP-76在CXCR 4介导的T淋巴细胞运输中的新作用。
Rapid arrest of T cells at target sites upon engagement of chemokine receptors is crucial to the proper functioning of the immune system. Although T cell arrest always occurs under hydrodynamic forces in vivo, most studies investigating the molecular mechanisms of arrest have been performed under static conditions. While the requirement of the adaptor protein SLP-76 in TCR-induced integrin activation has been demonstrated, its role in chemokine-triggered T cell adhesion is unknown. Using a flow chamber system, we show that SLP-76 plays an important role in regulating the transition from tethering and rolling to firm adhesion of T cells under physiological shear flow in response to CXCL12α SDF-1α); SLP-76-deficient primary T cells exhibited defective adhesion with a significant decrease in the number of firmly arrested cells. We further demonstrate the N-terminal phosphotyrosines of SLP-76 play a critical role in this T cell adhesion under flow. These findings reveal a novel role for SLP-76 in CXCR4-mediated T lymphocyte trafficking.
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DOI：
10.1084/jem.20111493
发表时间：
2012-02-13
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Block H;Herter JM;Rossaint J;Stadtmann A;Kliche S;Lowell CA;Zarbock A
通讯作者：
Zarbock A
影响因子：
3.6
作者：
Ebert, LA;Schaerli, P;Moser, B
通讯作者：
Moser, B
影响因子：
15.3
作者：
Maltzman, JS;Kovoor, L;Koretzky, GA
通讯作者：
Koretzky, GA
影响因子：
9.2
作者：
Liu, SK;Fang, N;McGlade, CJ
通讯作者：
McGlade, CJ
影响因子：
3.3
作者：
García-Bernal, D;Wright, N;Teixidó, J
通讯作者：
Teixidó, J