Abstract
Overproduction of immunoglobulin E (IgE) and T helper cell type 2 (TH2) cytokines, including interleukin 4 (IL-4), IL-5 and IL-13, can result in allergic disorders. Although it is known that IL-4 is critical to the polarization of naïve CD4+ T cells to a TH2 phenotype, both in vitro and in many in vivo systems, other factors that regulate in vivo IL-4 production and TH2 commitment are poorly understood. IL-18, an IL-1-like cytokine that requires cleavage with caspase-1 to become active, was found to increase IgE production in a CD4+ T cells-, IL-4- and STAT6-dependent fashion. IL-18 and T cell receptor-mediated stimulation could induce naïve CD4+ T cells to develop into IL-4-producing cells in vitro. Thus, caspase-1 and IL-18 may be critical in regulation of IgE production in vivo, providing a potential therapeutic target for allergic disorders.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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CD4-Positive T-Lymphocytes / immunology*
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CD40 Ligand / genetics
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Caspase 1 / genetics
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Caspase 1 / immunology
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Female
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Gene Expression
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Humans
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Immunoglobulin E / biosynthesis*
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Interleukin-18 / genetics
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Interleukin-18 / immunology*
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Interleukin-4 / genetics
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Interleukin-4 / immunology*
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Leprosy, Lepromatous / blood
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Leprosy, Lepromatous / immunology
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Leprosy, Tuberculoid / blood
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Leprosy, Tuberculoid / immunology
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Mice, Knockout
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Mice, Transgenic
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Receptors, Interleukin-4 / genetics
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Receptors, Interleukin-4 / immunology
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STAT6 Transcription Factor
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Th2 Cells / immunology
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Th2 Cells / physiology
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Trans-Activators / genetics
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Trans-Activators / immunology*
Substances
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Interleukin-18
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Receptors, Interleukin-4
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STAT6 Transcription Factor
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STAT6 protein, human
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Stat6 protein, mouse
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Trans-Activators
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CD40 Ligand
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Interleukin-4
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Immunoglobulin E
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Caspase 1