白细胞介素17
生物
转化生长因子β
转化生长因子
细胞生物学
白细胞介素21
白细胞介素2受体
白细胞介素3
细胞因子
免疫学
C-C趋化因子受体6型
T细胞
趋化因子
趋化因子受体
免疫系统
作者
Nicolas Manel,Derya Unutmaz,Dan R. Littman
摘要
TH-17 cells are interleukin 17 (IL-17)–secreting CD4+ T helper cells involved in autoimmune disease and mucosal immunity. In naive CD4+ T cells from mice, IL-17 is expressed in response to a combination of IL-6 or IL-21 and transforming growth factor-β (TGF-β) and requires induction of the nuclear receptor RORγt. It has been suggested that the differentiation of human TH-17 cells is independent of TGF-β and thus differs fundamentally from that in mice. We show here that TGF-β, IL-1β and IL-6, IL-21 or IL-23 in serum-free conditions were necessary and sufficient to induce IL-17 expression in naive human CD4+ T cells from cord blood. TGF-β upregulated RORγt expression but simultaneously inhibited its ability to induce IL-17 expression. Inflammatory cytokines relieved this inhibition and increased RORγt-directed IL-17 expression. Other gene products detected in TH-17 cells after RORγt induction included the chemokine receptor CCR6, the IL-23 receptor, IL-17F and IL-26. Our studies identify RORγt as having a central function in the differentiation of human TH-17 cells from naive CD4+ T cells and suggest that similar cytokine pathways are involved in this process in mice and humans.
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