The actin cloud induced by LFA-1-mediated outside-in signals lowers the threshold for T-cell activation
The actin cloud induced by LFA-1-mediated outside-in signals lowers the threshold for T-cell activation
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DOI：
10.1182/blood-2005-12-020164
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发表时间：
2007-01-01
期刊：
影响因子：
20.3
通讯作者：
Saito, Takashi
中科院分区：
文献类型：
--
作者：
Suzuki, Jun-ichiro;Yamasaki, Sho;Saito, Takashi
肌动蛋白细胞骨架的动态重排在T细胞受体(TCR)信号转导和免疫突触(IS)的形成中起着关键作用。在TCR刺激下T细胞中的肌动蛋白重排之后，我们发现了一种独特的肌动蛋白环状重组，称为“肌动蛋白云”，它是由外向内信号通过淋巴细胞功能相关抗原-1(LFA-1)的参与而特异性地诱导的。在T细胞-抗原提呈细胞(APC)的相互作用中，肌动蛋白云是在没有抗原的情况下产生的，定位于T细胞-APC界面的中心，在那里它积累了LFA-1和酪氨酸磷酸化的蛋白。LFA-1诱导的肌动蛋白云的形成涉及ADAP(黏附和脱颗粒促进适配器蛋白)的磷酸化、LFA-1/ADAP的组装和c-Jun氨基末端激酶(JNK)的激活，该过程不依赖于TCR及其近端信号。肌动蛋白云的形成降低了随后T细胞激活的门槛。因此，LFA-1参与诱导的肌动蛋白云可能是LFA-1介导的T细胞激活共刺激功能的可能平台。
The dynamic rearrangement of the actin cytoskeleton plays critical roles in T-cell receptor (TCR) signaling and immunological synapse (IS) formation in T cells. Following actin rearrangement in T cells upon TCR stimulation, we found a unique ring-shaped reorganization of actin called the "actin cloud," which was specifically induced by outside-in signals through lymphocyte function-associated antigen-1 (LFA-1) engagement. In T-cell-antigen-presenting cell (APC) interactions, the actin cloud is generated in the absence of antigen and localized at the center of the T-cell-APC interface, where it accumulates LFA-1 and tyrosine-phosphorylated proteins. The LFA-1-induced actin cloud formation involves ADAP (adhesion- and degranulation-promoting adaptor protein) phosphorylation, LFA-1/ADAP assembly, and c-Jun N-terminal kinase (JNK) activation, and occurs independent of TCR and its proximal signaling. The formation of the actin cloud lowers the threshold for subsequent T-cell activation. Thus, the actin cloud induced by LFA-1 engagement may serve as a possible platform for LFA-1-mediated costimulatory function for T-cell activation.