T17 细胞需要持续的经典 IL-6 受体信号来保持转录和功能特征。
T17 cells require ongoing classic IL-6 receptor signaling to retain transcriptional and functional identity.
机构信息
Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Department of Genetics, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
出版信息
Sci Immunol. 2020 Jul 17;5(49). doi: 10.1126/sciimmunol.aaw2262.
Abstract
Acting in concert with TGF-β, interleukin-6 (IL-6) signaling induces T helper 17 (T17) cell development by programming T17-related genes via signal transducers and activators of transcription 3 (STAT3). A role for IL-6 signaling beyond the inductive phase of T17 cell development has not been defined because IL-23 signaling downstream of T17 cell induction also activates STAT3 and is thought responsible for T17 cell maintenance. Here, we find that IL-6 signaling is required for both induction and maintenance of mouse T17 cells; IL-6Rα-deficient T17 cells rapidly lost their T17 phenotype and did not cause disease in two models of colitis. Cotransfer of wild-type T17 cells with IL-6Rα-deficient T17 cells induced colitis but was unable to rescue phenotype loss of the latter. High IL-6 expression in the colon promoted classic, or cis, rather than transreceptor signaling that was required for maintenance of T17 cells. Thus, ongoing classic IL-6 signaling underpins the T17 program and is required for T17 cell maintenance and function.
摘要
与 TGF-β协同作用，白细胞介素-6（IL-6）信号通过信号转导子和转录激活子 3（STAT3）对 T 辅助 17（T17）细胞相关基因进行编程，从而诱导 T17 细胞的发育。由于 T17 细胞诱导后的 IL-23 信号也会激活 STAT3，并且被认为负责 T17 细胞的维持，因此，IL-6 信号在 T17 细胞发育的诱导阶段之外的作用尚未确定。在这里，我们发现 IL-6 信号对于诱导和维持小鼠 T17 细胞是必需的；IL-6Rα 缺陷型 T17 细胞迅速失去 T17 表型，并且在两种结肠炎模型中均不会引起疾病。野生型 T17 细胞与 IL-6Rα 缺陷型 T17 细胞的共转移诱导了结肠炎，但无法挽救后者表型的丧失。结肠中高表达的 IL-6 促进了经典的顺式而不是反式受体信号，这对于 T17 细胞的维持是必需的。因此，持续的经典 IL-6 信号为 T17 程序提供支持，并且是 T17 细胞维持和功能所必需的。
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