RT Journal Article SR Electronic T1 Critical Role for STAT4 Activation by Type 1 Interferons in the Interferon-γ Response to Viral Infection JF Science JO Science FD American Association for the Advancement of Science SP 2063 OP 2066 DO 10.1126/science.1074900 VO 297 IS 5589 A1 Nguyen, Khuong B. A1 Watford, Wendy T. A1 Salomon, Rachelle A1 Hofmann, Sigrun R. A1 Pien, Gary C. A1 Morinobu, Akio A1 Gadina, Massimo A1 O'Shea, John J. A1 Biron, Christine A. YR 2002 UL http://science.sciencemag.org/content/297/5589/2063.abstract AB Interferons (IFNs) are essential for host defense. Although the antiviral effects of the type 1 IFNs IFN-α and IFN-β (IFN-α/β) have been established, their immunoregulatory functions, especially their ability to regulate IFN-γ production, are poorly understood. Here we show that IFN-α/β activate STAT4 directly (STAT, signal transducers and activators of transcription) and that this is required for IFN-γ production during viral infections of mice, in concert with T cell receptor–derived signals. In contrast, STAT1 appears to negatively regulate IFN-α/β induction of IFN-γ. Thus, type 1 IFNs, in addition to interleukin-12, provide pathways for innate regulation of adaptive immunity, and their immunoregulatory functions are controlled by modulating the activity of individual STATs.