Abstract
Btk plays crucial roles in the differentiation and activation of B and myeloid cells. Despite drastic reductions of other Ig isotypes, paradoxically high IgE responses have been known in btk mutant mice. Here we show that btk(-/-) dendritic cells exhibit a more mature phenotype and a stronger in vitro and in vivo T cell-stimulatory ability than wild-type cells. Increased IgE responses were induced by adoptive transfer of btk(-/-) dendritic cells into mice. Consistent with the stronger T cell-stimulatory ability of btk(-/-) dendritic cells, btk(-/-) mice exhibited enhanced inflammation in Th2-driven asthma and Th1-driven contact sensitivity experiments. These negative regulatory functions of Btk in dendritic cells appear to be mediated mainly through autocrine secretion of IL-10 and subsequent activation of Stat3.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
MeSH terms
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Adoptive Transfer
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Agammaglobulinaemia Tyrosine Kinase
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Animals
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Asthma / immunology
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Cell Differentiation / immunology*
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Dendritic Cells / cytology*
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Dendritic Cells / immunology*
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Dendritic Cells / metabolism
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Dermatitis, Contact / immunology
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Immunization
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Immunoblotting
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Immunoglobulin E / metabolism
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Interleukin-10 / immunology
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Interleukin-10 / metabolism*
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Mice
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Mice, Knockout
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Protein-Tyrosine Kinases / genetics
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Protein-Tyrosine Kinases / immunology
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Protein-Tyrosine Kinases / metabolism*
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STAT3 Transcription Factor / immunology
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STAT3 Transcription Factor / metabolism*
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T-Lymphocytes, Helper-Inducer / immunology*
Substances
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STAT3 Transcription Factor
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Stat3 protein, mouse
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Interleukin-10
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Immunoglobulin E
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Protein-Tyrosine Kinases
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Agammaglobulinaemia Tyrosine Kinase
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Btk protein, mouse