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

First Author  Kano S Year  2008
Journal  Nat Immunol Volume  9
Issue  1 Pages  34-41
PubMed ID  18059273 Mgi Jnum  J:130476
Mgi Id  MGI:3771755 Doi  10.1038/ni1538
Citation  Kano S, et al. (2008) The contribution of transcription factor IRF1 to the interferon-gamma-interleukin 12 signaling axis and TH1 versus TH-17 differentiation of CD4+ T cells. Nat Immunol 9(1):34-41
abstractText  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.
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