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Nsun2 coupling with RoRγt shapes the fate of Th17 cells and promotes colitis

Author

Listed:
  • Wen-Lan Yang

    (Chinese Academy of Sciences and China National Center for Bioinformation
    University of Chinese Academy of Sciences)

  • Weinan Qiu

    (Chinese Academy of Sciences and China National Center for Bioinformation
    University of Chinese Academy of Sciences, Chinese Academy of Sciences
    Shanghai Jiao Tong University School of Medicine)

  • Ting Zhang

    (Chinese Academy of Sciences and China National Center for Bioinformation
    Chinese Academy of Sciences)

  • Kai Xu

    (Chinese Academy of Sciences
    Chinese Academy of Sciences
    Beijing Institute for Stem Cell and Regenerative Medicine)

  • Zi-Juan Gu

    (University of Chinese Academy of Sciences, Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Yu Zhou

    (Nanjing Medical University)

  • Heng-Ji Xu

    (Chinese Academy of Sciences and China National Center for Bioinformation
    University of Chinese Academy of Sciences)

  • Zhong-Zhou Yang

    (Nanjing University Medical School)

  • Bin Shen

    (Nanjing Medical University)

  • Yong-Liang Zhao

    (Chinese Academy of Sciences and China National Center for Bioinformation
    University of Chinese Academy of Sciences)

  • Qi Zhou

    (Chinese Academy of Sciences
    Chinese Academy of Sciences
    Beijing Institute for Stem Cell and Regenerative Medicine)

  • Ying Yang

    (Chinese Academy of Sciences and China National Center for Bioinformation
    University of Chinese Academy of Sciences
    Chinese Academy of Sciences)

  • Wei Li

    (Chinese Academy of Sciences
    Chinese Academy of Sciences
    Beijing Institute for Stem Cell and Regenerative Medicine)

  • Peng-Yuan Yang

    (University of Chinese Academy of Sciences, Chinese Academy of Sciences)

  • Yun-Gui Yang

    (Chinese Academy of Sciences and China National Center for Bioinformation
    University of Chinese Academy of Sciences
    Chinese Academy of Sciences)

Abstract

T helper 17 (Th17) cells are a subset of CD4+ T helper cells involved in the inflammatory response in autoimmunity. Th17 cells secrete Th17 specific cytokines, such as IL-17A and IL17-F, which are governed by the master transcription factor RoRγt. However, the epigenetic mechanism regulating Th17 cell function is still not fully understood. Here, we reveal that deletion of RNA 5-methylcytosine (m5C) methyltransferase Nsun2 in mouse CD4+ T cells specifically inhibits Th17 cell differentiation and alleviates Th17 cell-induced colitis pathogenesis. Mechanistically, RoRγt can recruit Nsun2 to chromatin regions of their targets, including Il17a and Il17f, leading to the transcription-coupled m5C formation and consequently enhanced mRNA stability. Our study demonstrates a m5C mediated cell intrinsic function in Th17 cells and suggests Nsun2 as a potential therapeutic target for autoimmune disease.

Suggested Citation

  • Wen-Lan Yang & Weinan Qiu & Ting Zhang & Kai Xu & Zi-Juan Gu & Yu Zhou & Heng-Ji Xu & Zhong-Zhou Yang & Bin Shen & Yong-Liang Zhao & Qi Zhou & Ying Yang & Wei Li & Peng-Yuan Yang & Yun-Gui Yang, 2023. "Nsun2 coupling with RoRγt shapes the fate of Th17 cells and promotes colitis," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36595-w
    DOI: 10.1038/s41467-023-36595-w
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