Abstract
Recently, the transcription factor GATA-3 was shown to be selectively expressed in Th2 but not Th1 cells and to augment Th2-specific cytokines. Here, we show that loss of GATA-3 expression by developing Th1 cells requires IL-12 signaling through Stat4 and does not simply result from an absence of IL-4. Moreover, we demonstrate a novel role for GATA-3 in directly repressing Th1 development distinct from its positive actions on Th2-specific cytokines. GATA-3 inhibits Th1 cytokines by a cell-intrinsic mechanism that is not dependent on IL-4 and that may involve repression of IL-12 signaling. Thus, GATA-3 expression and IL-12 signaling are mutually antagonistic, which facilitates rapid dominance of one pathway during early Th development, producing a stable divergence in cytokine profiles.
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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CD4-Positive T-Lymphocytes / cytology
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DNA-Binding Proteins / physiology*
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GATA3 Transcription Factor
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Humans
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Interferon-gamma / biosynthesis
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Interleukin-2 / physiology
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Interleukin-4 / physiology*
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Mice
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Mice, Transgenic
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Receptors, Interleukin / biosynthesis
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Receptors, Interleukin-12
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STAT4 Transcription Factor
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Signal Transduction / physiology
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Th1 Cells / cytology*
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Th1 Cells / physiology
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Trans-Activators / physiology*
Substances
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DNA-Binding Proteins
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GATA3 Transcription Factor
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GATA3 protein, human
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Gata3 protein, mouse
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Interleukin-2
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Receptors, Interleukin
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Receptors, Interleukin-12
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STAT4 Transcription Factor
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STAT4 protein, human
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Stat4 protein, mouse
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Trans-Activators
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Interleukin-4
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Interferon-gamma