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

被引：114

作者：

Kano, Shin-ichi ^{[1
]}

Sato, Kojiro ^{[1
]}

Morishita, Yasyuki ^{[2
,3
]}

Vollstedt, Sabine ^{[1
]}

Kim, Sunhwa ^{[1
]}

Bishop, Keith ^{[4
,5
]}

Honda, Kenya ^{[1
]}

Kubo, Masato ^{[6
]}

Taniguchi, Tadatsugu ^{[1
]}

机构：

[1] Univ Tokyo, Dept Immunol, Bunkyo Ku, Tokyo 1130033, Japan

[2] Univ Tokyo, Grad Sch Med, Dept Pathol, Tokyo 1130033, Japan

[3] Univ Tokyo, Fac Med, Tokyo 1130033, Japan

[4] Univ Michigan, Sch Med, Grad Program Immunol, Ann Arbor, MI 48109 USA

[5] Univ Michigan, Sch Med, Dept Surg, Sect Gen Surg, Ann Arbor, MI 48109 USA

[6] RIKEN, Yokohama Inst, Res Ctr Allergey & Immunol, Lab Signal Network,Tsurumi Ku, Kanagawa 2300045, Japan

来源：

NATURE IMMUNOLOGY | 2008年 / 9卷 / 01期

关键词：

D O I：

10.1038/ni1538

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：34 / 41

页数：8

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