Department of Microbiology and Immunology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
Department of Dermatology, Hunan Key Laboratory of Medical Epigenomics, Second Xiangya Hospital, Central South University, Changsha, China.
J Autoimmun. 2017 Sep;83:113-121. doi: 10.1016/j.jaut.2017.07.002. Epub 2017 Jul 11.
Regulatory T cells (Tregs) are an essential cell subset for the maintenance of immune homeostasis. Foxp3 (Forkhead box P3) is the Treg master gene which is essential for immune suppressing activity. In addition, Tregs are characterized by a distinct pattern of gene expression, including upregulation of immune-suppressive genes and silencing of inflammatory genes. The molecular mechanisms of Treg development and maintenance have been intensively investigated. Tregs are characterized by expression of the transcription factor Foxp3. Several intronic enhancers and a promoter at the Foxp3 gene locus were shown to play important roles in Treg differentiation. The enhancers have been designated as conserved non-coding sequences (CNSs) 0, 1, 2, and 3. We showed that the transcription factors Nr4a and Smad2/3 are essential for the development of thymic Tregs and induced Tregs, respectively. Recently, Treg-specific DNA demethylation has been shown to play an important role in Treg stability. DNA demethylation of CNS2 has been implicated in Treg stability, and recent reports have revealed that the ten-eleven translocation (Tet) family of demethylation factor plays an important role in CpG demethylation at CNS2. This article reviews the recent progress on the roles of transcription factors and epigenetic modifications in the differentiation, maintenance, and function of Tregs.
调节性 T 细胞（Tregs）是维持免疫稳态的必需细胞亚群。叉头框蛋白 P3（Foxp3）是 Treg 的主基因，对于免疫抑制活性是必需的。此外，Tregs 的特征在于独特的基因表达模式，包括上调免疫抑制基因和沉默炎症基因。Treg 发育和维持的分子机制已得到深入研究。Tregs 表达转录因子 Foxp3。Foxp3 基因座的几个内含子增强子和启动子被证明在 Treg 分化中发挥重要作用。这些增强子被指定为保守非编码序列（CNS）0、1、2 和 3。我们表明，转录因子 Nr4a 和 Smad2/3 分别对于胸腺 Tregs 和诱导性 Tregs 的发育是必需的。最近，Treg 特异性 DNA 去甲基化在 Treg 稳定性中发挥重要作用。CNS2 的 DNA 去甲基化与 Treg 的稳定性有关，最近的报道揭示了十-十一易位（Tet）家族的去甲基化因子在 CNS2 的 CpG 去甲基化中发挥重要作用。本文综述了转录因子和表观遗传修饰在 Treg 分化、维持和功能中的作用的最新进展。
