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

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 TO differentiation by acting on II12rb1, the gene encoding the IL-12 receptor beta 1 subunit (IL-12R beta 1). IRF1 directly interacted with and activated the II12rb1 promoter in CD4(+) T cells. Notably, the IRF1-dependent induction of IL-12R beta 1 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-12R beta 1, our data suggest that distinct thresholds of IL-12R beta 1 expression are required for T(H)1 versus T-H-17 differentiation.