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

作者：Khuong B. Nguyen, Wendy T. Watford, Rachelle Salomon, Sigrun Ruth Hofmann, Gary C. Pien, Akio Morinobu, Massimo Gadina, John J. O’Shea, Christine A. Biron · 发表于：Science · 年份：2002 · DOI：10.1126/science.1074900 · 被引用次数：498 · 研究领域：Immune Cell Function and Interaction、Cytokine Signaling Pathways and Interactions、T-cell and B-cell Immunology

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.