The contribution of transcription factor IRF1 to the interferon-[gamma]- interleukin 12 signaling axis and T sub(H)1 versus T sub(H)-17 differentiation of CD4 super(+) T cells

Interleukin-12 (IL-12) and interferon-[gamma] (IFN-[gamma]) drive T helper type 1 (T sub(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 sub(H)1 differentiation by acting on Il12rb1, the gene encoding the IL-12 receptor [beta]1 subunit (IL- 12R[beta]1). IRF1 directly interacted with and activated the Il12rb1 promoter in CD4 super(+) 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 sub(H)1 versus T sub(H)-17 differentiation.