Abstract
Th cell differentiation is precisely regulated by thousands of genes at different stages. In the present study, we demonstrate that Dec2, a transcription factor belonging to the bHLH (basic helix-loop-helix) superfamily, is progressively induced during the course of Th2 differentiation, especially at the late stage. The up-regulated Dec2 can strongly promote Th2 development under Th2-inducing conditions, as evidenced by retrovirus-mediated gene transfer or transgenic manipulation. In addition, an enhancement of Th2 responses is also detectable in Dec2 transgenic mice in vivo. Conversely, RNA interference-mediated suppression of endogenous Dec2 could attenuate Th2 differentiation. Finally, we show that the enhanced Th2 development is at least in part due to substantial up-regulation of CD25 expression elicited by Dec2, thereby resulting in hyperresponsiveness to IL-2 stimulation.
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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CD4-Positive T-Lymphocytes / metabolism
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Cell Differentiation / immunology*
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Cytokines / immunology
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Cytokines / metabolism
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Female
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Interleukin-2 / immunology
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Interleukin-2 / metabolism
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Interleukin-4 / immunology
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Interleukin-4 / metabolism
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Lung / immunology
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Lung / metabolism
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Lung / pathology
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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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Ovalbumin / immunology
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RNA, Small Interfering / immunology
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RNA, Small Interfering / metabolism
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Receptors, Interleukin-2 / immunology*
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Receptors, Interleukin-2 / 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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Signal Transduction / immunology
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Th2 Cells / immunology*
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Th2 Cells / metabolism
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Transcription Factors / genetics
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Transcription Factors / immunology*
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Transcription Factors / metabolism
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Transfection
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Up-Regulation / immunology
Substances
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Bhlhb3 protein, mouse
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Cytokines
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Interleukin-2
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RNA, Small Interfering
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Receptors, Interleukin-2
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STAT6 Transcription Factor
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Stat6 protein, mouse
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Transcription Factors
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Interleukin-4
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Ovalbumin