Abstract
Pathogenic conversion of Th17 cells into multifunctional helper T cells or Th1 cells contributes to the pathogenesis of autoimmune diseases; however, the mechanism regulating the plasticity of Th17 cells remains unclear. Here, we found that Th17 cells expressed latent TGF-β1 in a manner dependent on autocrine TGF-β1. By employing IL-17-producing cell-specific Tgfb1 conditional knockout and fate-mapping systems, we demonstrated that TGF-β1-deficient Th17 cells are relatively susceptible to becoming IFN-γ producers through IL-12Rβ2 and IL-27Rα upregulation. TGF-β1-deficient Th17 cells exacerbated tissue inflammation compared to TGF-β1-sufficient Th17 cells in adoptive transfer models of experimental autoimmune encephalomyelitis and colitis. Thus, TGF-β1 production by Th17 cells provides an essential autocrine signal for maintaining the stability and regulating the pathogenicity of Th17 cells in vivo.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Autocrine Communication
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Autoimmunity*
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Biomarkers
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Colitis / etiology
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Colitis / metabolism
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Colitis / pathology
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Disease Susceptibility
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Encephalomyelitis, Autoimmune, Experimental / etiology
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Encephalomyelitis, Autoimmune, Experimental / metabolism
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Encephalomyelitis, Autoimmune, Experimental / pathology
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Gene Expression Regulation
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Immunomodulation*
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Immunophenotyping
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Lymphocyte Count
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Mice
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Mice, Transgenic
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Models, Biological
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Receptors, Interleukin / genetics
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Receptors, Interleukin / metabolism
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Receptors, Interleukin-12 / genetics
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Receptors, Interleukin-12 / metabolism
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T-Lymphocyte Subsets / immunology
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T-Lymphocyte Subsets / metabolism
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Th17 Cells / immunology*
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Th17 Cells / metabolism*
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Transforming Growth Factor beta1 / genetics
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Transforming Growth Factor beta1 / metabolism*
Substances
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Biomarkers
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Il12rb2 protein, mouse
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Il27ra protein, mouse
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Receptors, Interleukin
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Receptors, Interleukin-12
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Transforming Growth Factor beta1