Abstract
Stat4 is a key transcription factor involved in promoting cell-mediated immunity, whose expression in mature cells has been reported to be restricted to T and NK cells. We demonstrate here, however, that Stat4 expression is not restricted to lymphoid cells. In their basal state, monocytes do not express Stat4. Upon activation, however, IFN-gamma- and LPS-treated monocytes and dendritic cells express high levels of Stat4. Monocyte-expressed Stat4 in humans is phosphorylated in response to IFN-alpha, but not IL-12. In contrast, the Th2 cytokines, IL-4 and IL-10, specifically down-regulate Stat4 expression in activated monocytes, while having little effect on Stat6 expression. Moreover, macrophages in synovial tissue obtained from patients with rheumatoid arthritis express Stat4 in vivo, suggesting a potential role in a prototypical Th1-mediated human disease. IFN-alpha-induced Stat4 activation in human monocytes represents a previously unrecognized signaling pathway at sites of Th1 inflammation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Arthritis, Rheumatoid / immunology
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Arthritis, Rheumatoid / metabolism
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Arthritis, Rheumatoid / pathology*
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Cytokines / physiology
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DNA-Binding Proteins / antagonists & inhibitors
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DNA-Binding Proteins / biosynthesis*
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DNA-Binding Proteins / blood
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DNA-Binding Proteins / genetics
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Dendritic Cells / immunology
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Dendritic Cells / metabolism*
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Down-Regulation / immunology
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Humans
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Interferon-alpha / pharmacology
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Macrophage Activation*
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Macrophages / immunology
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Macrophages / metabolism*
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Macrophages / pathology
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Monocytes / immunology
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Monocytes / metabolism*
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Phosphorylation
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RNA, Messenger / biosynthesis
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RNA, Messenger / blood
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STAT4 Transcription Factor
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Synovial Membrane / immunology
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Synovial Membrane / metabolism
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Synovial Membrane / pathology
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Th1 Cells / immunology*
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Th1 Cells / metabolism
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Th2 Cells / immunology
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Trans-Activators / antagonists & inhibitors
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Trans-Activators / biosynthesis*
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Trans-Activators / blood
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Trans-Activators / genetics
Substances
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Cytokines
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DNA-Binding Proteins
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Interferon-alpha
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RNA, Messenger
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STAT4 Transcription Factor
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STAT4 protein, human
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Trans-Activators