Abstract
Type I IFNs induce gene expression through Stat1 and Stat2, which can in turn associate either to form Stat1 homodimers or the transcription factor ISGF-3. Stat1 homodimers also transduce signals for IFN-gamma. To explore the unique properties of Stat2 and ISGF-3 in type I IFN signaling, its gene was targeted for deletion. Stat2 null mice exhibit a number of defects in immune response. This includes an increased susceptibility to viral infection and the loss of a type I IFN autocrine/ paracrine loop, which in turn regulates several aspects of immune response. Intriguingly, Stat2-deficient fibroblasts exhibit a more significant defect in their response to type I IFNs than macrophages, highlighting tissue-specific differences in the response to this family of ligands.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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CD4-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / immunology
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / immunology*
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GTP Phosphohydrolases / genetics
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Gene Deletion
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Gene Expression
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Gene Targeting
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Interferon Regulatory Factor-1
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Interferon-Stimulated Gene Factor 3
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Interferon-Stimulated Gene Factor 3, gamma Subunit
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Interferon-alpha / immunology
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Interferon-gamma / immunology
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Mice
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Mice, Knockout
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Phosphoproteins / genetics
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Rhabdoviridae Infections / immunology
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STAT2 Transcription Factor
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Signal Transduction / immunology*
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Trans-Activators / immunology*
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Transcription Factors / genetics
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Vesicular stomatitis Indiana virus / immunology
Substances
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DNA-Binding Proteins
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Interferon Regulatory Factor-1
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Interferon-Stimulated Gene Factor 3
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Interferon-Stimulated Gene Factor 3, gamma Subunit
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Interferon-alpha
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Irf1 protein, mouse
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Isgf3g protein, mouse
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Phosphoproteins
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STAT2 Transcription Factor
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Stat2 protein, mouse
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Trans-Activators
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Transcription Factors
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Interferon-gamma
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GTP Phosphohydrolases