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Homeostatic Cytokines Drive Epigenetic Reprogramming of Activated T Cells into a "Naive-Memory" Phenotype.
iScience ( IF 5.8 ) Pub Date : 2020-03-19 , DOI: 10.1016/j.isci.2020.100989
Guido Frumento 1 , Kriti Verma 2 , Wayne Croft 3 , Andrea White 2 , Jianmin Zuo 2 , Zsuzsanna Nagy 4 , Stephen Kissane 5 , Graham Anderson 2 , Paul Moss 6 , Frederick E Chen 7
Affiliation  

Primary stimulation of T cells is believed to trigger unidirectional differentiation from naive to effector and memory subsets. Here we demonstrate that IL-7 can drive the phenotypic reversion of recently differentiated human central and effector memory CD8+ T cells into a naive-like phenotype.

These “naive-revertant” cells display a phenotype similar to that of previously reported stem cell memory populations and undergo rapid differentiation and functional response following secondary challenge. The chromatin landscape of reverted cells undergoes substantial epigenetic reorganization with increased accessibility for cytokine-induced mediators such as STAT and closure of BATF-dependent sites that drive terminal differentiation. Phenotypic reversion may at least partly explain the generation of “stem cell memory” CD8+ T cells and reveals cells within the phenotypically naive CD8+ T cell pool that are epigenetically primed for secondary stimulation. This information provides insight into mechanisms that support maintenance of T cell memory and may guide therapeutic manipulation of T cell differentiation.



中文翻译:

稳态细胞因子驱动活化的T细胞表观遗传重编程为“天真记忆”表型。

T细胞的初级刺激被认为触发了从幼稚到效应子和记忆子集的单向分化。在这里,我们证明IL-7可以驱动最近分化的人类中枢和效应记忆CD8 + T细胞的表型逆转为幼稚型表型。

这些“天然回复”细胞表现出与先前报道的干细胞记忆种群相似的表型,并在继发性攻击后经历快速分化和功能反应。还原细胞的染色质景观经历了实质性的表观遗传重组,增加了细胞因子诱导的介体(如STAT)的可及性,并封闭了驱动终末分化的BATF依赖性位点。表型逆转可能至少部分解释了“干细胞记忆” CD8 + T细胞的产生,并揭示了表型纯真的CD8 +中的细胞表观遗传的T细胞库可进行二次刺激。该信息提供了对支持T细胞记忆维持的机制的了解,并可能指导T细胞分化的治疗性操作。

更新日期:2020-03-19
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