Meyer J Friedman, Haram Lee, June-Yong Lee, Soohwan Oh
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引用次数: 0
摘要
Th细胞系的确定和功能特化与结合顺式调控元件的系决定转录因子(TF)的激活密切相关。这些决定Th细胞系的转录因子与多层转录调节因子协同作用,改变表观遗传景观,包括DNA甲基化、组蛋白修饰和三维染色体结构,以促进特定Th基因表达程序,从而实现表型多样化。越来越多的证据表明,Th 细胞分化并不像传统观点认为的那样僵化;相反,广泛的表型可塑性是 T 细胞系的固有特征。最近的研究已开始揭示从机制上控制 T 细胞亚群分化和免疫记忆的表观遗传学程序。下一代测序技术的进步使得对 CD4+ Th 细胞进行全局转录组学和表观基因组学研究成为可能,从而扩展了以前侧重于单个基因位点的研究结果。在这篇综述中,我们概述了最近对 CD4+ T 细胞介导的适应性免疫的转录和表观遗传调控的全基因组认识,并讨论了其对疾病和免疫疗法的影响。
Transcriptional and Epigenetic Regulation of Context-Dependent Plasticity in T-Helper Lineages.
Th cell lineage determination and functional specialization are tightly linked to the activation of lineage-determining transcription factors (TFs) that bind cis-regulatory elements. These lineage-determining TFs act in concert with multiple layers of transcriptional regulators to alter the epigenetic landscape, including DNA methylation, histone modification and three-dimensional chromosome architecture, in order to facilitate the specific Th gene expression programs that allow for phenotypic diversification. Accumulating evidence indicates that Th cell differentiation is not as rigid as classically held; rather, extensive phenotypic plasticity is an inherent feature of T cell lineages. Recent studies have begun to uncover the epigenetic programs that mechanistically govern T cell subset specification and immunological memory. Advances in next generation sequencing technologies have allowed global transcriptomic and epigenomic interrogation of CD4+ Th cells that extends previous findings focusing on individual loci. In this review, we provide an overview of recent genome-wide insights into the transcriptional and epigenetic regulation of CD4+ T cell-mediated adaptive immunity and discuss the implications for disease as well as immunotherapies.
期刊介绍:
Immune Network publishes novel findings in basic and clinical immunology and aims to provide a medium through which researchers in various fields of immunology can share and connect. The journal focuses on advances and insights into the regulation of the immune system and the immunological mechanisms of various diseases. Research that provides integrated insights into translational immunology is given preference for publication. All submissions are evaluated based on originality, quality, clarity, and brevity