自分泌信号
细胞生物学
RAR相关孤儿受体γ
生物
细胞分化
转录因子
白细胞介素3
信号转导
车站3
白细胞介素9
转化生长因子
白细胞介素15
白细胞介素
免疫学
受体
白细胞介素17
T细胞
细胞因子
白细胞介素21
免疫系统
FOXP3型
遗传学
基因
作者
Liang Zhou,Ivaylo I. Ivanov,Rosanne Spolski,Roy Min,Kevin Shenderov,Takeshi Egawa,David E. Levy,Warren J. Leonard,Dan R. Littman
摘要
T helper cells that produce interleukin 17 (IL-17; 'T(H)-17 cells') are a distinct subset of proinflammatory cells whose in vivo function requires IL-23 but whose in vitro differentiation requires only IL-6 and transforming growth factor-beta (TGF-beta). We demonstrate here that IL-6 induced expression of IL-21 that amplified an autocrine loop to induce more IL-21 and IL-23 receptor in naive CD4(+) T cells. Both IL-21 and IL-23, along with TGF-beta, induced IL-17 expression independently of IL-6. The effects of IL-6 and IL-21 depended on STAT3, a transcription factor required for the differentiation of T(H)-17 cells in vivo. IL-21 and IL-23 induced the orphan nuclear receptor RORgammat, which in synergy with STAT3 promoted IL-17 expression. IL-6 therefore orchestrates a series of 'downstream' cytokine-dependent signaling pathways that, in concert with TGF-beta, amplify RORgammat-dependent differentiation of T(H)-17 cells.
科研通智能强力驱动
Strongly Powered by AbleSci AI