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抗原经验性 CD8 T 细胞中细胞命运决定的转录控制。

Transcriptional Control of Cell Fate Determination in Antigen-Experienced CD8 T Cells.

机构信息

Department of Immunology and Microbiology, The Scripps Research Institute, Jupiter, Florida 33458, USA.

出版信息

Cold Spring Harb Perspect Biol. 2022 Feb 1;14(2):a037945. doi: 10.1101/cshperspect.a037945.

Abstract

Robust immunity to intracellular infections is mediated by antigen-specific naive CD8 T cells that become activated and differentiate into phenotypically and functionally diverse subsets of effector cells, some of which terminally differentiate and others that give rise to memory cells that provide long-lived protection. This developmental system is an outstanding model with which to elucidate how regulation of chromatin structure and transcriptional control establish gene expression programs that govern cell fate determination, insights from which are likely to be useful for informing the design of immunotherapeutic approaches to engineer durable immunity to infections and tumors. A unifying framework that describes how naive CD8 T cells develop into memory cells is still outstanding. We propose a model that incorporates a common early linear path followed by divergent paths that slowly lose capacity to interconvert and discuss classical and contemporary observations that support these notions, focusing on insights from transcriptional control and chromatin regulation.

摘要

针对细胞内感染的强大免疫力是由抗原特异性的初始 CD8 T 细胞介导的,这些细胞被激活并分化为表型和功能多样化的效应细胞亚群,其中一些细胞终末分化,而另一些细胞则产生记忆细胞,提供长期保护。这个发育系统是一个杰出的模型,可以阐明染色质结构和转录控制如何调节基因表达程序,从而决定细胞命运的决定,这些见解可能有助于为免疫治疗方法的设计提供信息,以工程化对感染和肿瘤的持久免疫力。一个描述初始 CD8 T 细胞如何发展为记忆细胞的统一框架仍然存在。我们提出了一个模型,该模型包含一个共同的早期线性途径,然后是逐渐失去相互转化能力的分歧途径,并讨论了支持这些概念的经典和当代观察结果,重点关注转录控制和染色质调节的见解。

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