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T 细胞的工作机制:转录后机制如何控制 T 细胞的动态平衡和激活。

T cells at work: How post-transcriptional mechanisms control T cell homeostasis and activation.

机构信息

Department of Hematopoiesis, Sanquin Research, Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Oncode Institute, Utrecht, The Netherlands.

Oncode Institute, Utrecht, The Netherlands.

出版信息

Eur J Immunol. 2021 Sep;51(9):2178-2187. doi: 10.1002/eji.202049055. Epub 2021 Jul 14.

Abstract

T cells are central players of the adaptive immune system by protecting us from recurring infections and by killing malignant cells. Protective T cell responses rely on the concerted production of effector molecules such as cytolytic mediators, granzymes, and perforins, as well as pro-inflammatory cytokines and chemokines. Once activated, T cells drastically change their gene expression and rapidly respond to insults by producing ample amounts of effector molecules. In the absence of antigen, T cells remain in a quiescent state and survey our body for possible pathogenic insults. Resting T cells are, however, not inert, but continuously regulate their protein production to survive and to be prepared for possible re-infections. Here, we review our current knowledge on the regulation of gene expression in activated and quiescent T cells. We specifically focus on post-transcriptional mechanisms that define the protein output and that allow dormant cells to undergo active signaling and selective translation, keeping them poised for activation. Finally, we discuss which signals drive T cell survival and their preparedness to respond to insults and which mechanisms are involved in these processes.

摘要

T 细胞是适应性免疫系统的核心成员,可保护我们免受反复感染和杀死恶性细胞。保护性 T 细胞反应依赖于效应分子(如细胞溶解介质、颗粒酶和穿孔素)以及促炎细胞因子和趋化因子的协同产生。T 细胞一旦被激活,其基因表达就会急剧改变,并通过产生大量效应分子迅速对刺激做出反应。在没有抗原的情况下,T 细胞仍处于静止状态,并监测我们的身体是否存在可能的致病入侵。然而,静止的 T 细胞并非没有活性,而是在不断调节其蛋白质的产生,以维持生存并为可能的再次感染做好准备。在这里,我们回顾了我们目前对激活和静止 T 细胞中基因表达调控的认识。我们特别关注定义蛋白质输出的转录后机制,这些机制允许休眠细胞进行主动信号传递和选择性翻译,使它们随时准备激活。最后,我们讨论了哪些信号驱动 T 细胞的存活及其对刺激的准备情况,以及哪些机制参与了这些过程。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bc1/8457102/16b7a1b264e9/EJI-51-2178-g001.jpg

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