Abstract
IL-4 promotes the differentiation of naive CD4+ T cells into IL-4-producing T helper 2 (Th2) cells. Previous work provided suggestive but not conclusive evidence that the transcription factor c-Maf directed the tissue-specific expression of IL-4. It was not known whether c-Maf controlled the transcription of other Th2 cytokine genes. To elucidate the role of c-Maf in vivo, we examined cytokine production in mice lacking c-Maf (c-maf(-/-)). CD4+ T cells and NK T cells from c-maf(-/-) mice were markedly deficient in IL-4 production. However, the mice produced normal levels of IL-13 and IgE, and, when differentiated in the presence of exogenous IL-4, c-maf(-/-) T cells produced approximately normal levels of other Th2 cytokines. We conclude that c-Maf has a critical and selective function in IL-4 gene transcription in vivo.
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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Cytokines / physiology*
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DNA-Binding Proteins / metabolism
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DNA-Binding Proteins / physiology*
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Immunoglobulin E / metabolism
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Interleukin-10 / genetics
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Interleukin-10 / metabolism
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Interleukin-13 / metabolism
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Interleukin-4 / biosynthesis*
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Interleukin-4 / pharmacology
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Interleukin-5 / genetics
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Interleukin-5 / metabolism
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Mice
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Mice, Inbred BALB C
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Mice, Mutant Strains
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Promoter Regions, Genetic / physiology
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins / physiology*
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Proto-Oncogene Proteins c-maf
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Spleen / cytology
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Spleen / drug effects
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Th2 Cells / immunology
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Th2 Cells / metabolism*
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Transcription Factors / metabolism
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Transcription Factors / physiology*
Substances
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Cytokines
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DNA-Binding Proteins
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Interleukin-13
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Interleukin-5
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Maf protein, mouse
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-maf
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Transcription Factors
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Interleukin-10
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Interleukin-4
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Immunoglobulin E