Abstract
Suppressor of cytokine signaling (Socs) 3 is a cytokine-inducible inhibitor with critical but selective cell-specific effects. We show that deficiency of Socs3 in T cells had minimal effects on differentiation of T cells to the T helper (Th) 1 or Th2 subsets; accordingly, Socs3 had no effect on IL-12-dependent signal transducer and activator of transcription (Stat) 4 phosphorylation or IL-4-dependent Stat6 phosphorylation. By contrast, Socs3 was found to be a major regulator of IL-23-mediated Stat3 phosphorylation and Th17 generation, and Stat3 directly binds to the IL-17A and IL-17F promoters. We conclude that Socs3 is an essential negative regulator of IL-23 signaling, inhibition of which constrains the generation of Th17 differentiation.
MeSH terms
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Animals
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CD4-Positive T-Lymphocytes / metabolism
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Cell Differentiation
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Cell Separation
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Interleukin-17 / metabolism*
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Interleukin-23
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Interleukin-23 Subunit p19
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Interleukins / metabolism
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Mice
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Mice, Inbred C57BL
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Phosphorylation
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Promoter Regions, Genetic
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STAT4 Transcription Factor / metabolism
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Signal Transduction
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Suppressor of Cytokine Signaling 3 Protein
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Suppressor of Cytokine Signaling Proteins / metabolism
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Suppressor of Cytokine Signaling Proteins / physiology*
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T-Lymphocytes / immunology
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T-Lymphocytes / metabolism*
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Transcriptional Activation
Substances
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IL23A protein, human
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Il23a protein, mouse
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Interleukin-17
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Interleukin-23
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Interleukin-23 Subunit p19
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Interleukins
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SOCS3 protein, human
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STAT4 Transcription Factor
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Suppressor of Cytokine Signaling 3 Protein
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Suppressor of Cytokine Signaling Proteins