Tcf1 预先编程了中央记忆性 CD8 T 细胞在回忆性应答期间糖酵解的动员。

Tcf1 preprograms the mobilization of glycolysis in central memory CD8 T cells during recall responses.

机构信息

Center for Discovery and Innovation, Hackensack University Medical Center, Nutley, NJ, USA.

Center for Public Health Genomics, University of Virginia School of Medicine, Charlottesville, VA, USA.

出版信息

Nat Immunol. 2022 Mar;23(3):386-398. doi: 10.1038/s41590-022-01131-3. Epub 2022 Feb 21.

Abstract

The mechanisms underlying the heightened protection mediated by central memory CD8 T (T) cells remain unclear. Here we show that the transcription factor Tcf1 was required in resting T cells to generate secondary effector CD8 T cells and to clear pathogens during recall responses. Recall stimulation of CD8 T cells caused extensive reprogramming of the transcriptome and chromatin accessibility, leading to rapid induction of glycolytic enzymes, cell cycle regulators and transcriptional regulators, including Id3. This cluster of genes did not require Tcf1 in resting CD8 T cells, but depended on Tcf1 for optimal induction and chromatin opening in recall-stimulated CD8 T cells. Tcf1 bound extensively to these recall-induced gene loci in resting CD8 T cells and mediated chromatin interactions that positioned these genes in architectural proximity with poised enhancers. Thus, Tcf1 preprogramed a transcriptional program that supported the bioenergetic and proliferative needs of CD8 T cells in case of a secondary challenge.

摘要

中央记忆性 CD8 T(T)细胞介导的增强保护作用的机制尚不清楚。在这里,我们表明转录因子 Tcf1 在静息 T 细胞中是产生次级效应 CD8 T 细胞和清除回忆反应期间病原体所必需的。CD8 T 细胞的回忆刺激导致转录组和染色质可及性的广泛重编程,导致糖酵解酶、细胞周期调节剂和转录调节剂的快速诱导,包括 Id3。这群基因在静息 CD8 T 细胞中不需要 Tcf1,但在回忆刺激的 CD8 T 细胞中,它们的最佳诱导和染色质开放依赖于 Tcf1。Tcf1 广泛结合于静息 CD8 T 细胞中的这些回忆诱导基因座,并介导染色质相互作用,使这些基因与处于启动状态的增强子在结构上接近。因此,Tcf1 预先编程了一个转录程序,以支持 CD8 T 细胞在二次挑战时的能量代谢和增殖需求。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/833e/8904300/d9374fc2943c/nihms-1769922-f0009.jpg

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