Lkb1 maintains Treg cell lineage identity

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 Zhou, Yongguang Yang, Guogang Xu, Tao Cheng () and Xiaoming Feng ()
Additional contact information
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
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

Nature Communications, 2017, vol. 8, issue 1, 1-14

Abstract: 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.

Date: 2017
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DOI: 10.1038/ncomms15876

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