The contribution of transcription factor IRF1 to the interferon-γ-interleukin 12 signaling axis and TH1 versus TH-17 differentiation of CD4+ T cells
The contribution of transcription factor IRF1 to the interferon-γ-interleukin 12 signaling axis and TH1 versus TH-17 differentiation of CD4+ T cells
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DOI：
10.1038/ni1538
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发表时间：
2008-01-01
影响因子：
30.5
通讯作者：
Taniguchi, Tadatsugu
中科院分区：
文献类型：
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作者：
Kano, Shin-ichi;Sato, Kojiro;Taniguchi, Tadatsugu
白细胞介素-12（IL-12）和干扰素-γ（IFN-γ）驱动T辅助细胞1型（T（H）1）分化，但参与这种分化的复杂基因网络的调节机制尚未完全了解。在这里，我们表明，IFN-γ诱导的转录因子IRF 1是必不可少的TO分化作用于II 12 rb 1，基因编码的IL-12受体β 1亚基（IL-12 R β 1）。IRF 1直接与CD 4（+）T细胞中的II 12 rb 1启动子相互作用并激活。值得注意的是，IL-12 R β 1的IRF 1依赖性诱导对于IFN-γ-IL-12信号传导是必需的，但对于IL-23-IL-17信号传导是不必要的。因为IL-12和IL-23都与IL-12 R β 1结合并通过IL-12 R β 1传递信号，我们的数据表明T（H）1与T-H-17分化需要不同的IL-12 R β 1表达阈值。
Interleukin-12 (IL-12) and interferon-gamma (IFN-gamma) drive T helper type 1 (T(H)1) differentiation, but the mechanisms underlying the regulation of the complicated gene networks involved in this differentiation are not fully understood. Here we show that the IFN-gamma-induced transcription factor IRF1 was essential in TO differentiation by acting on II12rb1, the gene encoding the IL-12 receptor beta 1 subunit (IL-12R beta 1). IRF1 directly interacted with and activated the II12rb1 promoter in CD4(+) T cells. Notably, the IRF1-dependent induction of IL-12R beta 1 was essential for IFN-gamma-IL-12 signaling but was dispensable for IL-23-IL-17 signaling. Because both IL-12 and IL-23 bind to and transmit signals through IL-12R beta 1, our data suggest that distinct thresholds of IL-12R beta 1 expression are required for T(H)1 versus T-H-17 differentiation.