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-big gamma–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

Interleukin-12 (IL-12) and interferon-gamma (IFN-gamma) 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-gamma-induced transcription factor IRF1 was essential in TH1 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 TH1 versus TH-17 differentiation.

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  1. Department of Immunology, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan
  2. Department of Pathology, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan.
  3. 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.
  4. 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

* In the version of this supplementary file originally posted online, a band in the middle panel of Fig. 4C was not visible; the contrast has been adjusted appropriately. The error has been corrected in the PDF version of the article.

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