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- Title
Critical role for STAT4 activation by type 1 interferons in the interferon-gamma response to viral infection.
- Authors
Nguyen, Khuong B; Watford, Wendy T; Salomon, Rachelle; Hofmann, Sigrun R; Pien, Gary C; Morinobu, Akio; Gadina, Massimo; O'Shea, John J; Biron, Christine A
- Abstract
Interferons (IFNs) are essential for host defense. Although the antiviral effects of the type 1 IFNs IFN-alpha and IFN-beta (IFN-alpha/beta) have been established, their immunoregulatory functions, especially their ability to regulate IFN-gamma production, are poorly understood. Here we show that IFN-alpha/beta activate STAT4 directly (STAT, signal transducers and activators of transcription) and that this is required for IFN-gamma production during viral infections of mice, in concert with T cell receptor-derived signals. In contrast, STAT1 appears to negatively regulate IFN-alpha/beta induction of IFN-gamma. 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.
- Publication
Science (New York, N.Y.), 2002, Vol 297, Issue 5589, p2063
- ISSN
1095-9203
- Publication type
Journal Article
- DOI
10.1126/science.1074900