Stable inhibitory activity of regulatory T cells requires the transcription factor Helios.
Stable inhibitory activity of regulatory T cells requires the transcription factor Helios.
复制标题
DOI：
10.1126/science.aad0616
复制
发表时间：
2015-10-16
期刊：
影响因子：
--
通讯作者：
Cantor H
中科院分区：
文献类型：
--
作者：
Kim HJ;Barnitz RA;Kreslavsky T;Brown FD;Moffett H;Lemieux ME;Kaygusuz Y;Meissner T;Holderried TA;Chan S;Kastner P;Haining WN;Cantor H
免疫稳态的维持需要调节性T细胞（Tcells）。鉴于其固有的自身反应性，TcB必须稳定地保持抑制性表型以避免自身免疫。我们报告，FoxP 3 + CD 4和Qa-1-限制性CD 8 T细胞的转录因子（TF）Helios的表达受损导致小鼠的调节活性缺陷和自身免疫。Helios缺陷型Treg在炎症反应期间发展不稳定的表型，其特征在于FoxP 3表达降低和继发于STAT 5途径活化减少的效应细胞因子表达增加。CD 8 Treg还需要Helios依赖性STAT 5活化以存活并防止终末T细胞分化。将Helios定义为在炎症反应中稳定调节性T细胞的关键转录因子，为调节性T细胞的核心特性提供了遗传学解释。
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.