小柯机器人

美国北卡罗莱纳大学教堂山分校Yisong Y. Wan研究团队发现，TGF-β超家族细胞因子激活素A在自身免疫性神经炎症过程中被诱导并驱动致病性Th17细胞分化。相关论文于2021年1月8日在线发表在《免疫》杂志上。

研究人员探索了激活素A（与TGF-β1密切相关的TGF-β超家族成员）在T17病原细胞分化中的T细胞内在作用。在患有复发缓解型多发性硬化的个体和患有实验性自身免疫性脑脊髓炎的小鼠中，激活素A的表达发生增加。白介素6和激活素A的刺激诱导了一个分子程序，该程序反映了致病性Th17细胞的程序，并被阻断了激活素A信号传导所抑制。T细胞中激活素A及其受体ALK4的遗传破坏在体外和体内损害致病性Th17细胞分化。

从机制上讲，TGF-β1-ALK5抑制了对病原Th17细胞分化至关重要的细胞外信号调节激酶（ERK）磷酸化，但激活素-A-ALK4信号却没有抑制。因此，激活素A驱动致病性Th17细胞分化，这暗示了激活素A-ALK4-ERK信号轴是Th17细胞相关疾病的治疗靶标。

据了解，Th17细胞具有致病性和非致病性功能。尽管细胞因子TGF-β1有助于Th17细胞分化，但对于生成致病性Th17细胞却是必不可少的。

附：英文原文

Title: The TGF-β superfamily cytokine Activin-A is induced during autoimmune neuroinflammation and drives pathogenic Th17 cell differentiation

Author: Bing Wu, Song Zhang, Zengli Guo, Yanmin Bi, Mingxia Zhou, Ping Li, Maryamsadat Seyedsadr, Xiaojiang Xu, Jian-liang Li, Silva Markovic-Plese, Yisong Y. Wan

Issue&Volume: 2021-01-08

Abstract: Th17 cells are known to exert pathogenic and non-pathogenic functions. Although thecytokine transforming growth factor β1 (TGF-β1) is instrumental for Th17 cell differentiation,it is dispensable for generation of pathogenic Th17 cells. Here, we examined the T cell-intrinsicrole of Activin-A, a TGF-β superfamily member closely related to TGF-β1, in pathogenicTh17 cell differentiation. Activin-A expression was increased in individuals withrelapsing-remitting multiple sclerosis and in mice with experimental autoimmune encephalomyelitis.Stimulation with interleukin-6 and Activin-A induced a molecular program that mirroredthat of pathogenic Th17 cells and was inhibited by blocking Activin-A signaling. Geneticdisruption of Activin-A and its receptor ALK4 in T cells impaired pathogenic Th17cell differentiation in vitro and in vivo. Mechanistically, extracellular-signal-regulated kinase (ERK) phosphorylation, whichwas essential for pathogenic Th17 cell differentiation, was suppressed by TGF-β1-ALK5but not Activin-A-ALK4 signaling. Thus, Activin-A drives pathogenic Th17 cell differentiation,implicating the Activin-A-ALK4-ERK axis as a therapeutic target for Th17 cell-relateddiseases.

DOI: 10.1016/j.immuni.2020.12.010

Source: https://www.cell.com/immunity/fulltext/S1074-7613(20)30538-0

Immunity：《免疫》，创刊于1994年。隶属于细胞出版社，最新IF：43.474
官方网址：https://www.cell.com/immunity/home
投稿链接：https://www.editorialmanager.com/immunity/default.aspx