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Development and Functional Modulation of Regulatory T Cells by Transcription Factors and Epigenetics

机译:转录因子和表观遗传学调节T细胞的开发和功能调节

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Regulatory T cells (Tregs) are essential for the maintenance of immune homeostasis. Studies of Treg are not only necessary for understanding the mechanism of immune homeostasis but also extremely useful for the development of treatments of various immune diseases. Forkhead box P3 (Foxp3) was identified as the master gene responsible for the immune-suppressing activity of Tregs. The promoter region and several intronic enhancers, designated conserved noncoding sequence (CNS) 0, 1, 2, and 3, at the Foxp3 gene locus have important roles in Foxp3 expression and Treg development. We demonstrated that transcription factors Nr4a and Smad2/3 are required for development of thymic Tregs and induced Tregs, respectively. In addition to transcription factors, Treg-specific DNA demethylation has been shown to be important for Treg stability. In particular, DNA demethylation of CNS2 was implicated in Treg stability, and members of the ten-eleven translocation family of demethylation factors were recently demonstrated to have important roles in 5 '-C-phosphate-G-3 ' demethylation at CNS2. This article summarizes recent findings regarding the roles of transcription factors and epigenetic modifications in the differentiation, maintenance, and function of Tregs. This review will facilitate clinical application of Tregs to diseases in the field of ophthalmology, including uveitis and age-related macular degeneration.
机译:调节性T细胞(Tregs)对于维持免疫稳态是必不可少的。 Treg的研究不仅需要了解免疫稳态的机制,而且对各种免疫疾病的治疗也非常有用。尖头箱P3(Foxp3)被鉴定为负责Tregs免疫抑制活性的主基因。启动子区域和几种内肠增强剂,在FoxP3基因位点处具有指定的保守的非编码序列(CNS)0,1,2和3,在FOXP3表达和Treg发育中具有重要作用。我们证明了转录因子NR4a和Smad2 / 3分别用于发育胸腺Tregs和诱导的Tregs。除了转录因子之外,已显示特异性特异性DNA去甲基化对Treg稳定性重要。特别地,CNS2的DNA去甲基化涉及Treg稳定性,并且最近将10-11级易位系列的去甲基化因子的成员在CNS2处具有5'-C磷酸-G-3'去甲基化的重要作用。本文总结了关于转录因子和表观遗传修饰在特雷格斯的分化,维护和功能中的作用的结果。本综述将促进Tregs Tregs对眼科领域的疾病的临床应用,包括葡萄膜炎和年龄相关的黄斑变性。

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