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

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

Research output: Contribution to journalArticle

86 Citations (Scopus)

Abstract

Interleukin-12 (IL-12) and interferon-γ (IFN-γ) 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-γ-induced transcription factor IRF1 was essential in TH1 differentiation by acting on Il12rb1, the gene encoding the IL-12 receptor β1 subunit (IL-12Rβ1). IRF1 directly interacted with and activated the Il12rb1 promoter in CD4+ T cells. Notably, the IRF1-dependent induction of IL-12Rβ1 was essential for IFN-γ-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-12Rβ1, our data suggest that distinct thresholds of IL-12Rβ1 expression are required for TH1 versus TH-17 differentiation.

Original languageEnglish
Pages (from-to)34-41
Number of pages8
JournalNature Immunology
Volume9
Issue number1
DOIs
Publication statusPublished - 2008 Jan
Externally publishedYes

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Interleukin-12 Receptors
Interleukin-12
Interferons
Transcription Factors
Interleukin-23
T-Lymphocytes
Interleukin-17
Gene Regulatory Networks
Genes

ASJC Scopus subject areas

  • Immunology

Cite this

The contribution of transcription factor IRF1 to the interferon-γ-interleukin 12 signaling axis and TH1 versus TH-17 differentiation of CD4+ T cells. / Kano, Shin Ichi; Sato, Kojiro; Morishita, Yasuyuki; Vollstedt, Sabine; Kim, Sunhwa; Bishop, Keith; Honda, Kenya; Kubo, Masato; Taniguchi, Tadatsugu.

In: Nature Immunology, Vol. 9, No. 1, 01.2008, p. 34-41.

Research output: Contribution to journalArticle

Kano, Shin Ichi ; Sato, Kojiro ; Morishita, Yasuyuki ; Vollstedt, Sabine ; Kim, Sunhwa ; Bishop, Keith ; Honda, Kenya ; Kubo, Masato ; Taniguchi, Tadatsugu. / The contribution of transcription factor IRF1 to the interferon-γ-interleukin 12 signaling axis and TH1 versus TH-17 differentiation of CD4+ T cells. In: Nature Immunology. 2008 ; Vol. 9, No. 1. pp. 34-41.
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