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Science 20 September 2002:
Vol. 297. no. 5589, pp. 2063 - 2066
DOI: 10.1126/science.1074900
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Reports

Critical Role for STAT4 Activation by Type 1 Interferons in the Interferon-gamma Response to Viral Infection

Khuong B. Nguyen,1* Wendy T. Watford,2* Rachelle Salomon,1 Sigrun R. Hofmann,2 Gary C. Pien,1 Akio Morinobu,2 Massimo Gadina,2 John J. O'Shea,2dagger Christine A. Biron1dagger ddagger

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.

1 Department of Molecular Microbiology and Immunology, Division of Biology and Medicine, Brown University, Providence, RI 02912, USA.
2 Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
*   These authors contributed equally to this work.

dagger    These authors contributed equally to this work.

ddagger    To whom correspondence should be addressed. E-mail: christine_biron{at}brown.edu

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