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Lkb1 maintains Treg cell lineage identity

Author

Listed:
  • Di Wu

    (State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College)

  • Yuechen Luo

    (State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College)

  • Wei Guo

    (State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College)

  • Qing Niu

    (State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College)

  • Ting Xue

    (Tongji Medical College, Huazhong University of Science and Technology)

  • Fei Yang

    (State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College)

  • Xiaolei Sun

    (State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College)

  • Song Chen

    (State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College)

  • Yuanyuan Liu

    (State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College)

  • Jingru Liu

    (Central Laboratory, The Union Hospital of Fujian Medical University, 29 Xinquan Road)

  • Zhina Sun

    (State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College)

  • Chunxiao Zhao

    (State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College)

  • Huifang Huang

    (Central Laboratory, The Union Hospital of Fujian Medical University, 29 Xinquan Road)

  • Fang Liao

    (Tongji Medical College, Huazhong University of Science and Technology)

  • Zhongchao Han

    (State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College)

  • Dongming Zhou

    (Institute Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences)

  • Yongguang Yang

    (First Hospital of Jilin University)

  • Guogang Xu

    (Chinese PLA General Hospital)

  • Tao Cheng

    (State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College)

  • Xiaoming Feng

    (State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College)

Abstract

Regulatory T (Treg) cells are a distinct T-cell lineage characterized by sustained Foxp3 expression and potent suppressor function, but the upstream dominant factors that preserve Treg lineage-specific features are mostly unknown. Here, we show that Lkb1 maintains Treg cell lineage identity by stabilizing Foxp3 expression and enforcing suppressor function. Upon T-cell receptor (TCR) stimulation Lkb1 protein expression is upregulated in Treg cells but not in conventional T cells. Mice with Treg cell-specific deletion of Lkb1 develop a fatal early-onset autoimmune disease, with no Foxp3 expression in most Treg cells. Lkb1 stabilizes Foxp3 expression by preventing STAT4-mediated methylation of the conserved noncoding sequence 2 (CNS2) in the Foxp3 locus. Independent of maintaining Foxp3 expression, Lkb1 programs the expression of a wide spectrum of immunosuppressive genes, through mechanisms involving the augmentation of TGF-β signalling. These findings identify a critical function of Lkb1 in maintaining Treg cell lineage identity.

Suggested Citation

  • Di Wu & Yuechen Luo & Wei Guo & Qing Niu & Ting Xue & Fei Yang & Xiaolei Sun & Song Chen & Yuanyuan Liu & Jingru Liu & Zhina Sun & Chunxiao Zhao & Huifang Huang & Fang Liao & Zhongchao Han & Dongming , 2017. "Lkb1 maintains Treg cell lineage identity," Nature Communications, Nature, vol. 8(1), pages 1-14, August.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15876
    DOI: 10.1038/ncomms15876
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    Cited by:

    1. Di Wu & Haomin Li & Mingwei Liu & Jun Qin & Yi Sun, 2022. "The Ube2m-Rbx1 neddylation-Cullin-RING-Ligase proteins are essential for the maintenance of Regulatory T cell fitness," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    2. David Bradley & Alan J. Smith & Alecia Blaszczak & Dharti Shantaram & Stephen M. Bergin & Anahita Jalilvand & Valerie Wright & Kathleen L. Wyne & Revati S. Dewal & Lisa A. Baer & Katherine R. Wright &, 2022. "Interferon gamma mediates the reduction of adipose tissue regulatory T cells in human obesity," Nature Communications, Nature, vol. 13(1), pages 1-12, December.

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