Article abstract
Nature Immunology 9, 34 - 41 (2008)
Published online: 2 December 2007 | Corrected online: 13 December 2007 | doi:10.1038/ni1538
The contribution of transcription factor IRF1 to the interferon-
–interleukin 12 signaling axis and TH1 versus TH-17 differentiation of CD4+ T cells
Shin-ichi Kano1, Kojiro Sato1, Yasuyuki Morishita2, Sabine Vollstedt1, Sunhwa Kim1, Keith Bishop3, Kenya Honda1, Masato Kubo4 & Tadatsugu Taniguchi1
Abstract
Interleukin-12 (IL-12) and interferon-
(IFN-) drive T helper type 1 (TH1) 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--induced transcription factor IRF1 was essential in TH1 differentiation by acting on Il12rb1, the gene encoding the IL-12 receptor 
1 subunit (IL-12R1). IRF1 directly interacted with and activated the Il12rb1 promoter in CD4+ T cells. Notably, the IRF1-dependent induction of IL-12R1 was essential for IFN-–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-12R1, our data suggest that distinct thresholds of IL-12R1 expression are required for TH1 versus TH-17 differentiation.
- Department of Immunology, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan
- Department of Pathology, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan.
- Section of General Surgery, Department of Surgery and the Graduate Program in Immunology, University of Michigan School of Medicine, University of Michigan Medical Center, Ann Arbor, Michigan 48109, USA.
- Laboratory for Signal Network, Research Center for Allergy and Immunology, RIKEN Yokohama Institute, Suehiro-cho 1-7-22, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
Correspondence to: Tadatsugu Taniguchi1 e-mail: tada@m.u-tokyo.ac.jp
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