Abstract
Interleukin (IL)-4 is a central regulator of T helper 2 (Th2) immune responses, and also has a major impact on innate immune cells. This cytokine primes macrophages for immune responses to parasites and induces a distinct macrophage phenotype that may also promote tissue repair. IL-4 signaling in macrophages is primarily mediated by the transcription factor signal transducer and activator of transcription 6 (Stat6), which in turn regulates a number of secondary DNA binding proteins that may participate in shaping the resulting phenotype. The impact of secondary transcription factors on IL-4-treated macrophages, however, is largely unknown. Here we show that interferon regulatory factor 4 (Irf4) is strongly induced on RNA and protein level in bone marrow-derived macrophages upon priming with IL-4. Using microarray-based whole genome expression analysis, we also demonstrate that a subset of IL-4 regulated genes, including several MHC-II genes, Ciita, Cyp1b1, and Il1rn, are dysregulated in Irf4-deficient macrophages. The presented data suggests a non-redundant role for Irf4 in shaping the phenotype of alternatively primed macrophages.
Copyright 2010 Elsevier GmbH. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Aryl Hydrocarbon Hydroxylases / genetics
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Aryl Hydrocarbon Hydroxylases / metabolism
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Cytochrome P-450 CYP1B1
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Gene Expression Regulation
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Immunity, Innate / genetics
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Interferon Regulatory Factors / genetics
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Interferon Regulatory Factors / immunology
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Interferon Regulatory Factors / metabolism*
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Interleukin 1 Receptor Antagonist Protein / genetics
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Interleukin 1 Receptor Antagonist Protein / metabolism
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Interleukin-4 / immunology
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Interleukin-4 / metabolism
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Macrophage Activation / genetics
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Macrophages / immunology
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Macrophages / metabolism*
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Macrophages / pathology
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Microarray Analysis
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism
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STAT6 Transcription Factor / genetics
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STAT6 Transcription Factor / immunology
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STAT6 Transcription Factor / metabolism*
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Trans-Activators / genetics
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Trans-Activators / metabolism
Substances
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Interferon Regulatory Factors
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Interleukin 1 Receptor Antagonist Protein
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MHC class II transactivator protein
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Nuclear Proteins
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STAT6 Transcription Factor
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Trans-Activators
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interferon regulatory factor-4
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Interleukin-4
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Aryl Hydrocarbon Hydroxylases
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Cyp1b1 protein, mouse
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Cytochrome P-450 CYP1B1