ChIP-Seq analysis of Helios and histone modifications in CD4+ and CD8+ Tregs

The maintenance of immune homeostasis requires regulatory T cells (Tregs). Given their intrinsic self-reactivity, Tregs must stably maintain a suppressive phenotype to avoid autoimmunity. We report that impaired expression of the transcription factor (TF) Helios by FoxP3+ CD4 and Qa-1-restricted CD8 Tregs results in defective regulatory activity and autoimmunity in mice. Helios-deficient Treg develop an unstable phenotype during inflammatory responses characterized by reduced FoxP3 expression and increased effector cytokine expression secondary to diminished activation of the STAT5 pathway. CD8 Treg also require Helios-dependent STAT5 activation for survival and to prevent terminal T cell differentiation. Definition of Helios as a key transcription factor that stabilizes regulatory T-cells in the face of inflammatory responses provides a genetic explanation for a core property of regulatory T-cells. This is an examination of the transcription factor Helios with 2 different histone modifications in both CD4+ and CD8+ Tregs. Appropriate control sequence files for ChIP input are also included.

免疫稳态的维持依赖调节性T细胞（regulatory T cells, Tregs）。鉴于其固有的自身反应性，调节性T细胞必须稳定维持其抑制表型，以避免自身免疫的发生。本研究报道，FoxP3+ CD4调节性T细胞与受Qa-1限制的CD8调节性T细胞中，转录因子（transcription factor, TF）Helios的表达受损，会导致小鼠出现调节活性缺陷与自身免疫。Helios缺陷的调节性T细胞在炎症应答过程中会发生表型不稳定，具体表现为FoxP3表达下调、效应细胞因子表达上调，该现象源于STAT5通路的激活水平减弱。CD8调节性T细胞同样需要Helios依赖的STAT5激活，以维持自身存活并阻止终末T细胞分化。明确Helios作为炎症应答环境下稳定调节性T细胞的关键转录因子，为阐释调节性T细胞的核心特性提供了遗传学依据。本研究针对CD4+与CD8+调节性T细胞中的两种不同组蛋白修饰，对转录因子Helios开展了检测；同时还包含了适用于ChIP输入的对照序列文件。