白细胞介素-27和干扰素-α通过信号转导和转录激活因子1（Stat1）及信号转导和转录激活因子3（Stat3）发出信号，并在初始T细胞中诱导T盒转录因子（T-Bet）和白细胞介素-12受体β2（IL-12Rβ2）。
IL-27 and IFN-alpha signal via Stat1 and Stat3 and induce T-Bet and IL-12Rbeta2 in naive T cells.
作者信息
Hibbert Linda, Pflanz Stefan, De Waal Malefyt Rene, Kastelein Robert A
机构信息
Department of Discovery Biology, DNAX Research Institute, Palo Alto, CA 94304, USA.
出版信息
J Interferon Cytokine Res. 2003 Sep;23(9):513-22. doi: 10.1089/10799900360708632.
Interleukin-27 (IL-27) supports proliferation of naive CD4(+) T cells and enhances interferon-gamma (IFN-gamma) production by activated T cells and natural killer (NK) cells. We report here that IL-27 induces Stat1 and Stat3 phosphorylation and activation in human and murine cell lines and primary human T cells. IL-27 also induces T-Bet, a Stat1-dependent gene crucial to Th1 cell commitment. Similarly, IFN-alpha activates Stat1 and Stat3 and T-Bet expression in naive T cells. Induction of T-Bet results in upregulation of IL-12Rbeta2 on naive T cells, which is essential for responsiveness to IL-12 and differentiation to a Th1 phenotype. Both IL-27 and IFN-alpha induce expression of IL-12Rbeta2 in T cells. In contrast, IFN-gamma, which activates Stat1 but not Stat3, induces expression of T-Bet but not IL-12Rbeta2 in naive T cells. We propose that IL-27 and IFN-alpha are important for early Th1 commitment and act upstream of IL-12 and IFN-gamma in this pathway.
白细胞介素-27（IL-27）可支持初始CD4(+) T细胞的增殖，并增强活化的T细胞和自然杀伤（NK）细胞产生干扰素-γ（IFN-γ）的能力。我们在此报告，IL-27可在人和小鼠细胞系以及原代人T细胞中诱导Stat1和Stat3的磷酸化及活化。IL-27还可诱导T-Bet，这是一种对Th1细胞分化至关重要的依赖Stat1的基因。同样，IFN-α可激活初始T细胞中的Stat1和Stat3以及T-Bet的表达。T-Bet的诱导导致初始T细胞上IL-12Rβ2的上调，这对于对IL-12的反应性及向Th1表型的分化至关重要。IL-27和IFN-α均可诱导T细胞中IL-12Rβ2的表达。相比之下，激活Stat1但不激活Stat3的IFN-γ可诱导初始T细胞中T-Bet的表达，但不诱导IL-12Rβ2的表达。我们提出，IL-27和IFN-α对于早期Th1分化很重要，并在此途径中在IL-12和IFN-γ的上游起作用。
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