Regulatory T cells (T_reg cells) perform two distinct functions: they maintain self-tolerance, and they support organ homeostasis by differentiating into specialized tissue T_reg cells. We found that epigenetic modifications defined the molecular characteristics of tissue T_reg cells. Tagmentation-based whole-genome bisulfite sequencing revealed more than 11,000 regions that were methylated differentially in pairwise comparisons of tissue T_reg cell populations and lymphoid T cells. Similarities in the epigenetic landscape led to the identification of a common tissue T_reg cell population that was present in many organs and was characterized by gain and loss of DNA methylation that included many gene sites associated with the T_H2 subset of helper T cells, such as the gene encoding cytokine IL-33 receptor ST2, as well as the production of tissue-regenerative factors. Furthermore, the ST2-expressing population was dependent on the transcriptional regulator BATF and could be expanded by IL-33. Thus, tissue T_reg cells integrate multiple waves of epigenetic reprogramming that define their tissue-restricted specialization.

中文翻译：

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全基因组DNA甲基化格局定义了组织中调节性T细胞的专业化

调节性T细胞（T _reg细胞）执行两种不同的功能：它们保持自我耐受，并通过分化成专门的组织T _reg细胞来支持器官稳态。我们发现表观遗传修饰定义了组织T _reg细胞的分子特征。基于标记的全基因组亚硫酸氢盐测序显示，在组织T _reg细胞群体和淋巴T细胞的成对比较中，有11,000多个区域甲基化差异。表观遗传学上的相似之处导致了对常见组织T _reg的鉴定存在于许多器官中的细胞群，其特征是DNA甲基化的得失，包括与辅助T细胞的T _H 2亚型相关的许多基因位点，例如编码细胞因子IL-33受体ST2的基因，以及组织再生因子的产生。此外，表达ST2的群体依赖于转录调节因子BATF，并且可以被IL-33扩增。因此，组织T _reg细胞整合了表观遗传重编程的多个波次，这些波定义了它们的组织受限特化。