Tespa1 is involved in late thymocyte development through the regulation of TCR-mediated signaling
Tespa1 is involved in late thymocyte development through the regulation of TCR-mediated signaling
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Tespa1 通过调节 TCR 介导的信号传导参与晚期胸腺细胞发育
DOI：
10.1038/ni.2301
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发表时间：
2012-06-01
影响因子：
30.5
通讯作者：
Lu, Linrong
中科院分区：
文献类型：
--
作者：
Wang, Di;Zheng, Mingzhu;Lu, Linrong
在CD 4（+）CD 8（+）双阳性发育阶段通过T细胞抗原受体（TCR）的信号传导决定胸腺细胞的选择和谱系定型。在这里，我们描述了一个以前未表征的T细胞表达的蛋白质，Tespa 1，在胸腺细胞的积极选择的关键功能。Tespa 1（-/-）小鼠的成熟胸腺CD 4（+）和CD 8（+）T细胞较少，这反映了胸腺细胞发育受损。Tespa 1与TCR信号传导组分PLC-γ 1和Grb 2相关，Tespa 1缺陷导致TCR信号传导减弱，如Erk-AP-1和Ca 2 +-NFAT途径的缺陷性激活所反映的。我们的研究结果表明，Tespa 1是TCR信号体的组成部分，并且在T细胞发育期间通过调节TCR信号传导对T细胞选择和成熟至关重要。
Signaling via the T cell antigen receptor (TCR) during the CD4(+)CD8(+) double-positive developmental stage determines thymocyte selection and lineage commitment. Here we describe a previously uncharacterized T cell-expressed protein, Tespa1, with critical functions during the positive selection of thymocytes. Tespa1(-/-) mice had fewer mature thymic CD4(+) and CD8(+) T cells, which reflected impaired thymocyte development. Tespa1 associated with the TCR signaling components PLC-gamma 1 and Grb2, and Tespa1 deficiency resulted in attenuated TCR signaling, as reflected by defective activation of the Erk-AP-1 and Ca2+-NFAT pathways. Our findings demonstrate that Tespa1 is a component of the TCR signalosome and is essential for T cell selection and maturation through the regulation of TCR signaling during T cell development.