Abstract
TGF-beta is an important immunomodulatory cytokine that can inhibit differentiation of effector T cells. In this report, we address the molecular mechanisms through which TGF-beta inhibits differentiation of CD4(+) cells into Th type 2 cells. We demonstrate that TGF-beta inhibits GATA-3 expression in developing Th cells. We also show that inhibition of GATA-3 expression by TGF-beta is a major mechanism of inhibition of Th2 differentiation by TGF-beta as ectopic expression of GATA-3 in developing T cells overcomes the ability of TGF-beta to inhibit Th2 differentiation. TGF-beta likely inhibits GATA-3 expression at the transcriptional level and does so without interfering with IL-4 signaling.
MeSH terms
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Adjuvants, Immunologic / physiology*
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Animals
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Cell Differentiation / immunology
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Cell Division / immunology
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DNA-Binding Proteins / antagonists & inhibitors*
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DNA-Binding Proteins / biosynthesis*
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DNA-Binding Proteins / genetics
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Enzyme-Linked Immunosorbent Assay
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GATA3 Transcription Factor
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Genetic Vectors / immunology
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Green Fluorescent Proteins
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Growth Inhibitors / physiology*
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Immunosuppressive Agents / pharmacology
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Interleukin-2 / pharmacology
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Interleukin-4 / biosynthesis
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Interleukin-4 / physiology
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Luminescent Proteins / biosynthesis
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Luminescent Proteins / genetics
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Lymphocyte Activation / immunology
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Mice
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Mice, Transgenic
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Retroviridae / genetics
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Retroviridae / immunology
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Signal Transduction / immunology
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Th2 Cells / cytology*
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Th2 Cells / immunology*
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Th2 Cells / metabolism
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Trans-Activators / antagonists & inhibitors*
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Trans-Activators / biosynthesis*
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Trans-Activators / genetics
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Transduction, Genetic
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Transforming Growth Factor beta / physiology*
Substances
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Adjuvants, Immunologic
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DNA-Binding Proteins
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GATA3 Transcription Factor
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Gata3 protein, mouse
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Growth Inhibitors
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Immunosuppressive Agents
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Interleukin-2
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Luminescent Proteins
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Trans-Activators
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Transforming Growth Factor beta
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Green Fluorescent Proteins
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Interleukin-4