转录因子IRF1对干扰素-γ-白细胞介素12信号轴以及CD4+ T细胞的TH1与TH17分化的作用。

The contribution of transcription factor IRF1 to the interferon-gamma-interleukin 12 signaling axis and TH1 versus TH-17 differentiation of CD4+ T cells.

作者信息

Kano Shin-ichi, Sato Kojiro, Morishita Yasuyuki, Vollstedt Sabine, Kim Sunhwa, Bishop Keith, Honda Kenya, Kubo Masato, Taniguchi Tadatsugu

机构信息

Department of Immunology, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan.

出版信息

Nat Immunol. 2008 Jan;9(1):34-41. doi: 10.1038/ni1538. Epub 2007 Dec 2.

DOI:10.1038/ni1538

PMID:18059273

Abstract

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 T(H)1 differentiation by acting on Il12rb1, the gene encoding the IL-12 receptor beta1 subunit (IL-12Rbeta1). IRF1 directly interacted with and activated the Il12rb1 promoter in CD4+ T cells. Notably, the IRF1-dependent induction of IL-12Rbeta1 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-12Rbeta1, our data suggest that distinct thresholds of IL-12Rbeta1 expression are required for T(H)1 versus T(H)-17 differentiation.

摘要

白细胞介素-12（IL-12）和干扰素-γ（IFN-γ）驱动1型辅助性T细胞（T(H)1）分化，但参与这种分化的复杂基因网络调控的潜在机制尚未完全了解。在此我们表明，IFN-γ诱导的转录因子IRF1通过作用于Il12rb1（编码IL-12受体β1亚基（IL-12Rβ1）的基因）在T(H)1分化中至关重要。IRF1在CD4+ T细胞中直接与Il12rb1启动子相互作用并激活它。值得注意的是，IRF1依赖的IL-12Rβ1诱导对于IFN-γ-IL-12信号传导至关重要，但对于IL-23-IL-17信号传导则是可有可无的。由于IL-12和IL-23都与IL-12Rβ1结合并通过其传递信号，我们的数据表明，T(H)1与T(H)-17分化需要不同阈值的IL-12Rβ1表达。