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

Academic Article

Abstract

  • 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 T(H)1 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 T(H)1 versus T(H)-17 differentiation.

    • Published In

  • Nature Immunology  Journal

    • Keywords

  • Animals, CD4-Positive T-Lymphocytes, Cell Differentiation, Cells, Cultured, Interferon Regulatory Factor-1, Interferon-gamma, Interleukin-12, Interleukin-17, Interleukin-23, Lymphocyte Activation, Mice, Mice, Knockout, Promoter Regions, Genetic, Receptors, Interleukin-12, Signal Transduction, Th1 Cells

    • Digital Object Identifier (doi)

    Author List

  • Kano S-I; Sato K; Morishita Y; Vollstedt S; Kim S; Bishop K; Honda K; Kubo M; Taniguchi T

    • Start Page

  • 34

    • End Page

  • 41

    • Volume

  • 9

    • Issue

  • 1