机构：[1]Department of General Surgery, Ruijin Hospital,Department of Immunology and Microbiology, State Key Laboratory of Systems Medicine for Cancer, Shanghai Jiao Tong University School of Medicine, Shanghai, China[2]Department of Shanghai Institute of Immunology, Department of Immunology and Microbiology, State Key Laboratory of Systems Medicine for Cancer, Shanghai Jiao Tong University School of Medicine, Shanghai, China[3]Center for Cancer Immunology, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong Province, China[4]Central Laboratory, Hebei Collaborative Innovation Center of Tumor Microecological Metabolism Regulation, Affiliated Hospital of Hebei University, Baoding, Hebei Province, China河北大学附属医院[5]Innovative Institute of Chinese Medicine and Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, China
The functional integrity of Treg cells is interwoven with cellular metabolism; however, the mechanisms governing Treg cell metabolic programs remain elusive. Here, we identified that the deubiquitinase USP47 inhibited RNA m6A reader YTHDF1-mediated c-Myc translation to maintain Treg cell metabolic and functional homeostasis. USP47 positively correlated with the tumor-infiltrating Treg cell signature in colorectal cancer and gastric cancer patient samples. USP47 ablation compromised Treg cell homeostasis and function in vivo, resulting in the development of inflammatory disorders, and boosted antitumor immune responses. USP47 deficiency in Treg cells triggered the accumulation of the c-Myc protein and in turn exacerbated hyperglycolysis. Mechanistically, USP47 prevented YTHDF1 ubiquitination to attenuate the association of YTHDF1 with translation initiation machinery, thereby decreasing m6A-based c-Myc translation efficiency. Our findings reveal that USP47 directs m6A-dependent metabolic programs to orchestrate Treg cell homeostasis and suggest novel approaches for selective immune modulation in cancer and autoimmune diseases by targeting USP47.
基金：
National Key
Research and Development Program of China (2021YFA1301402,
2020YFA0803603), the National Natural Science Foundation of
China (81930040, 82225020, 32200728, and 82274575), and
the Guangdong Basic and Applied Basic Research Foundation
(2021A1515110375).
第一作者机构：[1]Department of General Surgery, Ruijin Hospital,Department of Immunology and Microbiology, State Key Laboratory of Systems Medicine for Cancer, Shanghai Jiao Tong University School of Medicine, Shanghai, China[2]Department of Shanghai Institute of Immunology, Department of Immunology and Microbiology, State Key Laboratory of Systems Medicine for Cancer, Shanghai Jiao Tong University School of Medicine, Shanghai, China[3]Center for Cancer Immunology, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong Province, China
共同第一作者：
通讯作者：
通讯机构：[1]Department of General Surgery, Ruijin Hospital,Department of Immunology and Microbiology, State Key Laboratory of Systems Medicine for Cancer, Shanghai Jiao Tong University School of Medicine, Shanghai, China[2]Department of Shanghai Institute of Immunology, Department of Immunology and Microbiology, State Key Laboratory of Systems Medicine for Cancer, Shanghai Jiao Tong University School of Medicine, Shanghai, China[4]Central Laboratory, Hebei Collaborative Innovation Center of Tumor Microecological Metabolism Regulation, Affiliated Hospital of Hebei University, Baoding, Hebei Province, China[5]Innovative Institute of Chinese Medicine and Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, China[*1]Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai 200025, China[*2]Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai 200025, China[*3]Innovative Institute of Chinese Medicine and Pharmacy, Shandong University of Traditional Chinese Medicine, 4655 Daxue Road, Changqing District, Jinan 250399, China.[*4]Central Laboratory,Hebei Collaborative Innovation Center of Tumor Microecological Metabolism Regulation, Affiliated Hospital of Hebei University, 212 Yuhua East Road, Baoding 071000, Hebei, China.
推荐引用方式(GB/T 7714)：
Aiting Wang,Haiyan Huang,Jian-Hong Shi,et al.USP47 inhibits m6A-dependent c-Myc translation to maintain regulatory T cell metabolic and functional homeostasis[J].JOURNAL OF CLINICAL INVESTIGATION.2023,133(23):doi:10.1172/JCI169365.
APA：
Aiting Wang,Haiyan Huang,Jian-Hong Shi,Xiaoyan Yu,Rui Ding...&Qiang Zou.(2023).USP47 inhibits m6A-dependent c-Myc translation to maintain regulatory T cell metabolic and functional homeostasis.JOURNAL OF CLINICAL INVESTIGATION,133,(23)
MLA：
Aiting Wang,et al."USP47 inhibits m6A-dependent c-Myc translation to maintain regulatory T cell metabolic and functional homeostasis".JOURNAL OF CLINICAL INVESTIGATION 133..23(2023)
医学