Year: 2017
Type: article
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.
Source: Nature Communications
DOI: 10.1038/ncomms15876
Authors: 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, Xiaoming Feng
Institutions: Chinese Academy of Medical Sciences & Peking Union Medical College, Institute of Hematology & Blood Diseases Hospital, State Key Laboratory of Experimental Hematology, Huazhong University of Science and Technology, Fujian Medical University, Union Hospital, Chinese Academy of Sciences, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, First Hospital of Jilin University, Chinese PLA General Hospital
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
OpenAlex ID: W2625855762