Modulation of cytokine receptors by IL-2 broadly regulates differentiation into helper T cell lineages.
Modulation of cytokine receptors by IL-2 broadly regulates differentiation into helper T cell lineages.
复制标题
作者：
辅助 T (TH) 细胞控制宿主对病原体的防御。 TH1、TH2 和 TH17 分化分别需要 IL-12、IL-4 和 IL-6 受体。 IL-2 信号通过转录因子 STAT5 通过调节 TH2 细胞因子基因簇和 Il4ra 表达来控制 TH2 分化。在这里，我们表明 IL-2 调节 TH1 分化，诱导 STAT5 依赖性 IL-12Rβ2 和 T-bet 表达，当 IL-2 被阻断时，人类 TH1 分化受损。小鼠 Il2−/− T 细胞中的 TH1 分化也受到损害，但通过 IL-12Rβ2 表达得以恢复。与 IL-2 对 TH17 分化的抑制作用一致，IL-2 降低了 Il6ra 和 Il6st 的表达，而即使当 IL-2 存在时，Il6st 也会增强 TH17 的分化。因此，IL-2 通过调节细胞因子受体表达来影响 TH 细胞分化，以帮助指定和维持分化状态。
T helper (TH) cells control host-defense to pathogens. The receptors for IL-12, IL-4, and IL-6 are required for TH1, TH2, and TH17 differentiation, respectively. IL-2 signaling via the transcription factor STAT5 controls TH2 differentiation by regulating the TH2 cytokine gene cluster and Il4ra expression. Here we show that IL-2 regulates TH1 differentiation, inducing STAT5-dependent IL-12Rβ2 and T-bet expression, with impaired human TH1 differentiation when IL-2 was blocked. TH1 differentiation was also impaired in mouse Il2−/− T cells but restored by IL-12Rβ2 expression. Consistent with IL-2’s inhibition of TH17 differentiation, IL-2 decreased Il6ra and Il6st expression, and Il6st augmented TH17 differentiation even when IL-2 was present. Thus, IL-2 influences TH cell differentiation by modulating cytokine receptor expression to help specify and maintain differentiated states.