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

doi:10.1038/ni1538

The contribution of transcription factor IRF1 to the interferon-γ-interleukin 12 signaling axis and T_H1 versus T_H-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 journal › Article › peer-review

95 Scopus citations

Abstract

Interleukin-12 (IL-12) and interferon-γ (IFN-γ) drive T helper type 1 (T_H1) 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 T_H1 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 T_H1 versus T_H-17 differentiation.

Original language	English (US)
Pages (from-to)	34-41
Number of pages	8
Journal	Nature Immunology
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/ni1538
State	Published - Jan 2008
Externally published	Yes

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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

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.",

author = "Kano, {Shin Ichi} and Kojiro Sato and Yasuyuki Morishita and Sabine Vollstedt and Sunhwa Kim and Keith Bishop and Kenya Honda and Masato Kubo and Tadatsugu Taniguchi",

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AU - Kano, Shin Ichi

AU - Sato, Kojiro

AU - Morishita, Yasuyuki

AU - Vollstedt, Sabine

AU - Kim, Sunhwa

AU - Bishop, Keith

AU - Honda, Kenya

AU - Kubo, Masato

AU - Taniguchi, Tadatsugu

PY - 2008/1

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N2 - 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.

AB - 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.

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The contribution of transcription factor IRF1 to the interferon-γ-interleukin 12 signaling axis and T_H1 versus T_H-17 differentiation of CD4⁺ T cells

Abstract

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