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多梳蛋白家族通过表观遗传调控 T 细胞。

Epigenetic regulation of T cells by Polycomb group proteins.

机构信息

Instituto de Microbiologia Paulo de Góes, Departamento de Imunologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.

Center for Cancer Cell Biology, Immunology and Infection, Discipline of Microbiology and Immunology, Rosalind Franklin University of Medicine and Science, Chicago, Illinois, USA.

出版信息

J Leukoc Biol. 2022 Jun;111(6):1253-1267. doi: 10.1002/JLB.2RI0122-039R. Epub 2022 Apr 25.

Abstract

T cells are critical for pathogen elimination, tumor surveillance, and immunoregulation. The development, activation, and differentiation of CD8 and CD4 T lymphocytes are a set of complex and dynamically regulated events that require epigenetic control. The Polycomb group (PcG) proteins are a family of diverse and evolutionarily conserved epigenetic modulators fundamentally involved in several mechanisms of gene regulation. PcG proteins can assemble into distinct repressor complexes, the two most understood being the Polycomb Repressor Complex (PRC)1 and PRC2, which control chromatin structure mainly through posttranslational modifications of histones. In this review, we will summarize the most recent findings regarding the diverse roles performed by PcG proteins in T cell biology. We will focus on PRC1 and PRC2 contribution to the regulation of T cell development in the thymus, CD4 T cell differentiation in helper or regulatory phenotypes and CD8 T cell fate commitment in the context of infections and cancer, highlighting the known mechanisms and knowledge gaps that still need to be addressed.

摘要

T 细胞对于病原体清除、肿瘤监测和免疫调节至关重要。CD8 和 CD4 T 淋巴细胞的发育、激活和分化是一组复杂且动态调节的事件,需要表观遗传控制。多梳蛋白家族(PcG)蛋白是一组多样化且进化上保守的表观遗传调节剂,它们主要通过组蛋白的翻译后修饰来参与几种基因调控机制。PcG 蛋白可以组装成不同的抑制复合物,其中两个最被理解的是多梳抑制复合物(PRC)1 和 PRC2,它们主要通过组蛋白的翻译后修饰来控制染色质结构。在这篇综述中,我们将总结 PcG 蛋白在 T 细胞生物学中发挥的多种作用的最新发现。我们将重点介绍 PRC1 和 PRC2 对 T 细胞在胸腺中的发育、辅助或调节表型中 CD4 T 细胞分化以及感染和癌症背景下 CD8 T 细胞命运决定的调控作用,强调已知的机制和仍需要解决的知识空白。

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