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USP21 prevents the generation of T-helper-1-like Treg cells

Author

Listed:
  • Yangyang Li

    (Key Laboratory of Molecular Virology and Immunology, CAS Center for Excellence in Molecular Cell Science, Unit of Molecular Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences)

  • Yue Lu

    (School of Pharmacy, Shanghai University of Traditional Chinese Medicine)

  • Shuaiwei Wang

    (Key Laboratory of Molecular Virology and Immunology, CAS Center for Excellence in Molecular Cell Science, Unit of Molecular Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences)

  • Zhijun Han

    (Chinese Academy of Sciences-Max Planck Society (MPG) Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences)

  • Fuxiang Zhu

    (Key Laboratory of Molecular Virology and Immunology, CAS Center for Excellence in Molecular Cell Science, Unit of Molecular Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences)

  • Yingmeng Ni

    (Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University)

  • Rui Liang

    (Key Laboratory of Molecular Virology and Immunology, CAS Center for Excellence in Molecular Cell Science, Unit of Molecular Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences)

  • Yan Zhang

    (Key Laboratory of Molecular Virology and Immunology, Unit of Hematopoietic Stem Cell and Transgenic Animal Model, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences)

  • Qibin Leng

    (Key Laboratory of Molecular Virology and Immunology, Unit of Immune Regulation, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences)

  • Gang Wei

    (Chinese Academy of Sciences-Max Planck Society (MPG) Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences)

  • Guochao Shi

    (Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University)

  • Ruihong Zhu

    (Flow Cytometry Core Facility, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences)

  • Dan Li

    (Key Laboratory of Molecular Virology and Immunology, CAS Center for Excellence in Molecular Cell Science, Unit of Molecular Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences)

  • Haikun Wang

    (Key Laboratory of Molecular Virology and Immunology, Unit of the Regulation of Immune Cell Differentiation, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences)

  • Song Guo Zheng

    (Clinical Immunology Center, Third Affiliated Hospital at Sun Yat-Sen University
    Penn State University Hershey College of Medicine)

  • Hongxi Xu

    (School of Pharmacy, Shanghai University of Traditional Chinese Medicine)

  • Andy Tsun

    (Key Laboratory of Molecular Virology and Immunology, CAS Center for Excellence in Molecular Cell Science, Unit of Molecular Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences
    Innovent Biologics (Suzhou) Co., Ltd)

  • Bin Li

    (Key Laboratory of Molecular Virology and Immunology, CAS Center for Excellence in Molecular Cell Science, Unit of Molecular Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences
    Shanghai Institute of Immunology, Shanghai JiaoTong University School of Medicine
    Shanghai JiaoTong University School of Medicine)

Abstract

FOXP3+ Regulatory T (Treg) cells play a key role in the maintenance of immune homeostasis and tolerance. Disruption of Foxp3 expression results in the generation of instable Treg cells and acquisition of effector T-cell-like function. Here we report that the E3 deubiquitinase USP21 prevents the depletion of FOXP3 at the protein level and restricts the generation of T-helper-1-like Treg cells. Mice depleted of Usp21 specifically in Treg cells display immune disorders characterized by spontaneous T-cell activation and excessive T-helper type 1 (Th1) skewing of Treg cells into Th1-like Treg cells. USP21 stabilizes FOXP3 protein by mediating its deubiquitination and maintains the expression of Treg signature genes. Our results demonstrate how USP21 prevents FOXP3 protein depletion and controls Treg lineage stability in vivo.

Suggested Citation

  • Yangyang Li & Yue Lu & Shuaiwei Wang & Zhijun Han & Fuxiang Zhu & Yingmeng Ni & Rui Liang & Yan Zhang & Qibin Leng & Gang Wei & Guochao Shi & Ruihong Zhu & Dan Li & Haikun Wang & Song Guo Zheng & Hong, 2016. "USP21 prevents the generation of T-helper-1-like Treg cells," Nature Communications, Nature, vol. 7(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms13559
    DOI: 10.1038/ncomms13559
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    Cited by:

    1. Xinnan Liu & Weiqi Zhang & Yichao Han & Hao Cheng & Qi Liu & Shouyu Ke & Fangming Zhu & Ying Lu & Xin Dai & Chuan Wang & Gonghua Huang & Bing Su & Qiang Zou & Huabing Li & Wenyi Zhao & Lianbo Xiao & L, 2024. "FOXP3+ regulatory T cell perturbation mediated by the IFNγ-STAT1-IFITM3 feedback loop is essential for anti-tumor immunity," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

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