{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T07:05:29Z","timestamp":1792047929893,"version":"4.4.0"},"reference-count":28,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5589","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[2002,9,20]]},"abstract":"<jats:p>Interferons (IFNs) are essential for host defense. Although the antiviral effects of the type 1 IFNs IFN-\u03b1 and IFN-\u03b2 (IFN-\u03b1\/\u03b2) have been established, their immunoregulatory functions, especially their ability to regulate IFN-\u03b3 production, are poorly understood. Here we show that IFN-\u03b1\/\u03b2 activate STAT4 directly (STAT, signal transducers and activators of transcription) and that this is required for IFN-\u03b3 production during viral infections of mice, in concert with T cell receptor\u2013derived signals. In contrast, STAT1 appears to negatively regulate IFN-\u03b1\/\u03b2 induction of IFN-\u03b3. 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.<\/jats:p>","DOI":"10.1126\/science.1074900","type":"journal-article","created":{"date-parts":[[2002,9,19]],"date-time":"2002-09-19T17:22:20Z","timestamp":1032456140000},"page":"2063-2066","source":"Crossref","is-referenced-by-count":420,"title":["Critical Role for STAT4 Activation by Type 1 Interferons in the Interferon-\u03b3 Response to Viral Infection"],"prefix":"10.1126","volume":"297","author":[{"given":"Khuong B.","family":"Nguyen","sequence":"first","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Division of Biology and Medicine, Brown University, Providence, RI 02912, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy T.","family":"Watford","sequence":"additional","affiliation":[{"name":"Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachelle","family":"Salomon","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Division of Biology and Medicine, Brown University, Providence, RI 02912, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sigrun R.","family":"Hofmann","sequence":"additional","affiliation":[{"name":"Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary C.","family":"Pien","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Division of Biology and Medicine, Brown University, Providence, RI 02912, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akio","family":"Morinobu","sequence":"additional","affiliation":[{"name":"Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Gadina","sequence":"additional","affiliation":[{"name":"Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John J.","family":"O'Shea","sequence":"additional","affiliation":[{"name":"Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine A.","family":"Biron","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Division of Biology and Medicine, Brown University, Providence, RI 02912, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.17.1.189"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.18.1.451"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(01)00154-6"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.2.634"},{"key":"e_1_3_1_6_2","doi-asserted-by":"crossref","first-page":"4298","DOI":"10.4049\/jimmunol.160.9.4298","volume":"160","author":"McRae B. 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Watford S. R. Hofmann A. Morinobu J. J. O'Shea unpublished observations."},{"key":"e_1_3_1_19_2","unstructured":"Materials and methods are available as supporting material on Science Online."},{"key":"e_1_3_1_20_2","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.4049\/jimmunol.156.3.1138","volume":"156","author":"Orange J. S.","year":"1996","unstructured":"Orange J. S., Biron C. A., J. Immunol. 156, 1138 (1996).","journal-title":"J. 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K.B.N is supported by a U.S. Department of Education GAANN (Graduate Assistantships in Areas of National Need) training grant R.S. is supported by NIH F31-GM20760-02 and G.C.P. is supported by a predoctoral fellowship from the Howard Hughes Medical Institute. We thank T. Salazar-Mather M. Dalod and W. 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