T细胞早期发育过程中E蛋白对TCR重排和表达的直接调控。

IF 5.4 3区 材料科学 Q2 CHEMISTRY, PHYSICAL
ACS Applied Energy Materials Pub Date : 2022-11-01 Epub Date: 2022-07-18 DOI:10.1002/wsbm.1578
Michele K Anderson, Juliana Dutra Barbosa da Rocha
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引用次数: 0

摘要

γδT细胞广泛分布于粘膜和上皮细胞丰富的组织中,是IL-17对几种病原体反应的重要早期来源。与αβT细胞一样,γδT细胞在胸腺中经历一个逐步的发育过程,需要重组基因组编码的片段来组装成熟的T细胞受体(TCR)基因。这一过程在多个层面上受到严格控制,以实现TCR片段组装,同时防止在这一过程中发生的双链DNA断裂所固有的基因组不稳定性。每个TCR基因座在结构和需求方面都有独特的方面,在αβ/γδT细胞命运选择前后有不同类型的调节。众所周知,Runx和Myb是TCRγ和TCRδ表达的关键转录调控因子,但E蛋白在TCRγ、TCRδ调控中的作用尚不清楚。多种证据表明,E蛋白在许多不同水平上参与TCR的表达,包括Rag重组酶基因表达和蛋白稳定性的调节、种系V段表达的诱导、染色质重塑以及胎儿和成人γδTCR库的限制。重要的是,E蛋白直接与TCRγ和TCRδ基因座的顺式调节元件相互作用,控制细胞成为αβT细胞或γδT细胞的倾向,甚至在决定TCR信号事件的谱系之前。这篇文章分类在:免疫系统疾病>干细胞和发育免疫系统疾病>遗传学/基因组学/表观遗传学。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Direct regulation of TCR rearrangement and expression by E proteins during early T cell development.

Direct regulation of TCR rearrangement and expression by E proteins during early T cell development.

γδ T cells are widely distributed throughout mucosal and epithelial cell-rich tissues and are an important early source of IL-17 in response to several pathogens. Like αβ T cells, γδ T cells undergo a stepwise process of development in the thymus that requires recombination of genome-encoded segments to assemble mature T cell receptor (TCR) genes. This process is tightly controlled on multiple levels to enable TCR segment assembly while preventing the genomic instability inherent in the double-stranded DNA breaks that occur during this process. Each TCR locus has unique aspects in its structure and requirements, with different types of regulation before and after the αβ/γδ T cell fate choice. It has been known that Runx and Myb are critical transcriptional regulators of TCRγ and TCRδ expression, but the roles of E proteins in TCRγ and TCRδ regulation have been less well explored. Multiple lines of evidence show that E proteins are involved in TCR expression at many different levels, including the regulation of Rag recombinase gene expression and protein stability, induction of germline V segment expression, chromatin remodeling, and restriction of the fetal and adult γδTCR repertoires. Importantly, E proteins interact directly with the cis-regulatory elements of the TCRγ and TCRδ loci, controlling the predisposition of a cell to become an αβ T cell or a γδ T cell, even before the lineage-dictating TCR signaling events. This article is categorized under: Immune System Diseases > Stem Cells and Development Immune System Diseases > Genetics/Genomics/Epigenetics.

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来源期刊
ACS Applied Energy Materials
ACS Applied Energy Materials Materials Science-Materials Chemistry
CiteScore
10.30
自引率
6.20%
发文量
1368
期刊介绍: ACS Applied Energy Materials is an interdisciplinary journal publishing original research covering all aspects of materials, engineering, chemistry, physics and biology relevant to energy conversion and storage. The journal is devoted to reports of new and original experimental and theoretical research of an applied nature that integrate knowledge in the areas of materials, engineering, physics, bioscience, and chemistry into important energy applications.
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