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.