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CD4 derived double negative T cells prevent the development and progression of nonalcoholic steatohepatitis

Author

Listed:
  • Guangyong Sun

    (Capital Medical University
    Capital Medical University
    Beijing Clinical Research Institute
    Beijing Key Laboratory of Tolerance Induction and Organ Protection in Transplantation)

  • Xinyan Zhao

    (National Clinical Research Center for Digestive Diseases)

  • Mingyang Li

    (Capital Medical University
    Beijing Clinical Research Institute
    Beijing Key Laboratory of Tolerance Induction and Organ Protection in Transplantation
    Capital Medical University)

  • Chunpan Zhang

    (Capital Medical University
    Beijing Clinical Research Institute
    Beijing Key Laboratory of Tolerance Induction and Organ Protection in Transplantation
    Capital Medical University)

  • Hua Jin

    (Capital Medical University
    Beijing Clinical Research Institute
    Beijing Key Laboratory of Tolerance Induction and Organ Protection in Transplantation
    Capital Medical University)

  • Changying Li

    (Capital Medical University
    Beijing Clinical Research Institute
    Beijing Key Laboratory of Tolerance Induction and Organ Protection in Transplantation
    Capital Medical University)

  • Liwei Liu

    (National Clinical Research Center for Digestive Diseases)

  • Yaning Wang

    (Capital Medical University
    Beijing Clinical Research Institute
    Beijing Key Laboratory of Tolerance Induction and Organ Protection in Transplantation
    Capital Medical University)

  • Wen Shi

    (Capital Medical University
    Beijing Clinical Research Institute
    Beijing Key Laboratory of Tolerance Induction and Organ Protection in Transplantation
    Capital Medical University)

  • Dan Tian

    (Capital Medical University
    Beijing Clinical Research Institute
    Beijing Key Laboratory of Tolerance Induction and Organ Protection in Transplantation
    Capital Medical University)

  • Hufeng Xu

    (Capital Medical University
    Beijing Clinical Research Institute
    Beijing Key Laboratory of Tolerance Induction and Organ Protection in Transplantation
    Capital Medical University)

  • Yue Tian

    (Capital Medical University
    Beijing Clinical Research Institute
    Beijing Key Laboratory of Tolerance Induction and Organ Protection in Transplantation
    Capital Medical University)

  • Yongle Wu

    (Capital Medical University)

  • Kai Liu

    (Capital Medical University
    Beijing Clinical Research Institute
    Beijing Key Laboratory of Tolerance Induction and Organ Protection in Transplantation
    Capital Medical University)

  • Zhongtao Zhang

    (Capital Medical University
    Beijing Key Laboratory of Tolerance Induction and Organ Protection in Transplantation
    National Clinical Research Center for Digestive Diseases)

  • Dong Zhang

    (Capital Medical University
    Capital Medical University
    Beijing Clinical Research Institute
    Beijing Key Laboratory of Tolerance Induction and Organ Protection in Transplantation)

Abstract

Hepatic inflammation is the driving force for the development and progression of NASH. Treatment targeting inflammation is believed to be beneficial. In this study, adoptive transfer of CD4+ T cells converted double negative T cells (cDNT) protects mice from diet-induced liver fat accumulation, lobular inflammation and focal necrosis. cDNT selectively suppress liver-infiltrating Th17 cells and proinflammatory M1 macrophages. IL-10 secreted by M2 macrophages decreases the survival and function of cDNT to protect M2 macrophages from cDNT-mediated lysis. NKG2A, a cell inhibitory molecule, contributes to IL-10 induced apoptosis and dampened suppressive function of cDNT. In conclusion, ex vivo-generated cDNT exert potent protection in diet induced obesity, type 2 diabetes and NASH. The improvement of outcome is due to the inhibition on liver inflammatory cells. This study supports the concept and the feasibility of potentially utilizing this autologous immune cell-based therapy for the treatment of NASH.

Suggested Citation

  • Guangyong Sun & Xinyan Zhao & Mingyang Li & Chunpan Zhang & Hua Jin & Changying Li & Liwei Liu & Yaning Wang & Wen Shi & Dan Tian & Hufeng Xu & Yue Tian & Yongle Wu & Kai Liu & Zhongtao Zhang & Dong Z, 2021. "CD4 derived double negative T cells prevent the development and progression of nonalcoholic steatohepatitis," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-20941-x
    DOI: 10.1038/s41467-021-20941-x
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