A critical role for Th17 cell-derived TGF-β1 in regulating the stability and pathogenicity of autoimmune Th17 cells
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:53 |
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| Enthalten in: |
Experimental & molecular medicine - 53(2021), 5 vom: 28. Mai, Seite 993-1004 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Choi, Garam [VerfasserIn] |
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| Links: |
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| Themen: |
Biomarkers |
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| Anmerkungen: |
Date Completed 24.03.2022 Date Revised 19.04.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s12276-021-00632-9 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM325989656 |
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| 245 | 1 | 2 | |a A critical role for Th17 cell-derived TGF-β1 in regulating the stability and pathogenicity of autoimmune Th17 cells |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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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| 700 | 1 | |a Kim, Daehong |e verfasserin |4 aut | |
| 700 | 1 | |a Kang, Chang-Yuil |e verfasserin |4 aut | |
| 700 | 1 | |a Chung, Yeonseok |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Byung-Seok |e verfasserin |4 aut | |
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