Dual functions for the endoplasmic reticulum calcium sensors STIM1 and STIM2 in T cell activation and tolerance
Dual functions for the endoplasmic reticulum calcium sensors STIM1 and STIM2 in T cell activation and tolerance
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DOI：
10.1038/ni1574
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发表时间：
2008-04-01
影响因子：
30.5
通讯作者：
Rao, Anjana
中科院分区：
文献类型：
--
作者：
Oh-hora, Masatsugu;Yamashita, Megumi;Rao, Anjana
通过钙释放激活的钙通道的钙库操作的钙内流是增加免疫细胞中细胞内钙的主要机制。在这里，我们表明，小鼠T细胞和成纤维细胞缺乏钙传感器STIM1严重受损的钙池操作的Ca2+内流，而缺乏钙传感器STIM2有一个较小的影响。然而，缺乏STIM1或STIM2的T细胞的细胞因子产生和转录因子NFAT的核转位要少得多。STIM1和STIM2的T细胞特异性消融导致显著的淋巴增殖表型和调节性T细胞数量的选择性减少。我们的结论是，无论是STIM1和STIM2促进存储操作的Ca2+进入T细胞和成纤维细胞，STIM蛋白的发展和调节T细胞的功能是必需的。
Store-operated Ca2+ entry through calcium release-activated calcium channels is the chief mechanism for increasing intracellular Ca2+ in immune cells. Here we show that mouse T cells and fibroblasts lacking the calcium sensor STIM1 had severely impaired store-operated Ca2+ influx, whereas deficiency in the calcium sensor STIM2 had a smaller effect. However, T cells lacking either STIM1 or STIM2 had much less cytokine production and nuclear translocation of the transcription factor NFAT. T cell-specific ablation of both STIM1 and STIM2 resulted in a notable lymphoproliferative phenotype and a selective decrease in regulatory T cell numbers. We conclude that both STIM1 and STIM2 promote store-operated Ca2+ entry into T cells and fibroblasts and that STIM proteins are required for the development and function of regulatory T cells.