STING信号通路激活,抑制T细胞增殖

JOURNAL OF EXPERIMENTAL MEDICINE

2017-05-08Article

11.991

影响因子

原标题:STING,先天性免疫应答感应器,抑制T淋巴细胞的增殖

① TMEM173编码STING,TMEM173突变患者由于组成性激活STING,T淋巴细胞增殖受损,记忆细胞(memory cell)数量减少;② STING激活后从ER转移到高尔基体,引起有丝分裂错误而抑制细胞增殖;③ 表达人体存在的STINGHAQ(抑制STING活性)可抑制STINGV155M(激活STING活性)从ER转移到高尔基体,恢复CD4+T细胞增殖;④ STING激活减少T淋巴细胞的增殖与TBK1和IRF3募集和I型IFN无关,靠其C末端结构域激活NF-κB行驶功能。

STING蛋白 适应性免疫反应 先天性免疫反应

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Title:
Intrinsic antiproliferative activity of the innate sensor STING in T lymphocytes

DOI:
10.1084/jem.20161674

Abstract & Authors展开

Abstract:
Activation of the cyclic dinucleotide sensor stimulator of interferon (IFN) genes (STING) is critical for IFN and inflammatory gene expression during innate immune responses. However, the role of STING in adaptive immunity is still unknown. In this study, we show that STING activation reduces the proliferation of T lymphocytes. This activity was independent of TBK1 and IRF3 recruitment and of type I IFN but required a distinct C-terminal domain of STING that activates NF-κB. Inhibition of cell proliferation by STING required its relocalization to the Golgi apparatus and caused mitotic errors. T lymphocytes from patients carrying constitutive active mutations in TMEM173 encoding STING showed impaired proliferation and reduced numbers of memory cells. Endogenous STING inhibited proliferation of mouse T lymphocytes. Therefore, STING, a critical innate sensor, also functions intrinsically in cells of the adaptive immune system to inhibit proliferation.

All Authors:
Silvia Cerboni,Nadia Jeremiah,Matteo Gentili,Ulf Gehrmann,Cécile Conrad,Marie-Claude Stolzenberg,Capucine Picard,Bénédicte Neven,Alain Fischer,Sébastian Amigorena,Frédéric Rieux-Laucat,Nicolas Manel

First Authors:
Silvia Cerboni,Nadia Jeremiah,Matteo Gentili,Ulf Gehrmann

Correspondence:
Frédéric Rieux-Laucat,Nicolas Manel

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