Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Department of Genetics, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Sci Immunol. 2020 Jul 17;5(49). doi: 10.1126/sciimmunol.aaw2262.
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.
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。
