Critical role of the transcription factors IRF1 and BATF in preparing the chromatin landscape during Type 1 regulatory cell differentiation [ATAC-seq]

Type 1 regulatory T (Tr1) cells are induced by interleukin-27 (IL-27) and have critical roles in the control of autoimmunity and resolution of inflammation. Here, we show that the transcription factors IRF1 and BATF are induced early during treatment with IL-27 and are required for the differentiation and function of Tr1 cells in vitro and in vivo. Epigenetic and transcriptional analyses reveal that both transcription factors influence chromatin accessibility and expression of genes required for Tr1 cell function. IRF1 and BATF deficiencies uniquely alter the chromatin landscape, suggesting that these factors serve a pioneering function during Tr1 cell differentiation. Chromatin accessibility (ATAC-seq) analysis of IL27-induced CD4 cells (WT, IRF1 KO, AHR KO, MAF KO, and BATF KO)

1型调节性T细胞（Type 1 regulatory T cells，Tr1）由白细胞介素27（interleukin-27，IL-27）诱导产生，在自身免疫调控与炎症消退过程中发挥关键作用。本研究证实，转录因子IRF1与BATF在IL-27处理早期即被诱导表达，且在体外与体内环境中均为Tr1细胞的分化与功能所必需。表观遗传与转录组分析显示，这两种转录因子均可调控Tr1细胞功能相关基因的染色质开放性及表达水平。IRF1与BATF的缺失会特异性重塑染色质开放图谱，提示二者在Tr1细胞分化过程中发挥先驱因子功能。本研究针对IL-27诱导的CD4阳性T细胞开展了染色质开放性分析（ATAC-seq，转座酶可及性测序），涉及野生型（WT）、IRF1基因敲除（IRF1 KO）、AHR基因敲除（AHR KO）、MAF基因敲除（MAF KO）及BATF基因敲除（BATF KO）各组样本。