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

作者：Kano Shin ichi; Sato Kojiro; Morishita Yasyuki; Vollstedt Sabine; Kim Sunhwa; Bishop Keith; Honda Kenya; Kubo Masato; Taniguchi Tadatsugu^*

来源：Nature Immunology, 2008, 9(1): 34-41.

DOI：10.1038/ni1538

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.

• 出版日期2008-1