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 types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Arenaviridae Infections / immunology*
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CD8-Positive T-Lymphocytes / immunology*
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CD8-Positive T-Lymphocytes / metabolism
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Cells, Cultured
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DNA-Binding Proteins / metabolism*
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Female
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Gene Expression Regulation
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Interferon Type I / immunology*
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Interferon Type I / pharmacology
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Interferon-gamma / biosynthesis*
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Interferon-gamma / genetics
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Interleukin-12 / physiology
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Lymphocytic choriomeningitis virus*
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Male
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Mice
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Mice, Inbred C57BL
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Phosphorylation
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Promoter Regions, Genetic
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Receptors, Antigen, T-Cell / immunology
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Receptors, Antigen, T-Cell / metabolism
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Recombinant Proteins
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STAT1 Transcription Factor
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STAT4 Transcription Factor
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Signal Transduction
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Th1 Cells / immunology
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Th1 Cells / metabolism
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Trans-Activators / metabolism*
Substances
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DNA-Binding Proteins
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Interferon Type I
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Receptors, Antigen, T-Cell
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Recombinant Proteins
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STAT1 Transcription Factor
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STAT4 Transcription Factor
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Stat1 protein, mouse
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Stat4 protein, mouse
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Trans-Activators
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Interleukin-12
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Interferon-gamma