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KMID : 0620920210530050993
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Experimental & Molecular Medicine
2021 Volume.53 No. 5 p.993 ~ p.1004
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A critical role for Th17 cell-derived TGF-β1 in regulating the stability and pathogenicity of autoimmune Th17 cells
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Choi Ga-Ram
Park Young-Jun
Cho Min-Kyoung
Moon Hee-Su
Kim Dae-Hong
Kang Chang-Yuil
Chung Yeon-Seok
Kim Byung-Seok
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Abstract
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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.
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KEYWORD
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Autoimmunity, Neuroimmunology
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