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Urolithin A Hijacks ERK1/2-ULK1 Cascade to Improve CD8+ T Cell Fitness for Antitumor Immunity

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收录情况： ◇ SCIE

作者：
Ma Shuaiya[1] * ; Wu Qi[2] ; Wu Wenxian[1,3,4] ; Tian Ye[1] ; Zhang Jie[5] ; Chen Chaojia[1] ; Sheng Xue[1] ; Zhao Fangcheng[1] ; Ding Lu[1] ; Wang Taixia[6] ; Zhao Laixi[1] ; Xie Yuying[3] ; Wang Yongxiang[3] ; Yue Xuetian[7] ; Wu Zhuanchang[1] ; Wei Jian[8] ; Zhang Kun[6] ; Liang Xiaohong[1] ; Gao Lifen[1] ; Wang Hongyan[9] ; Wang Guihua[2] ; Li Chunyang[10] ; Ma Chunhong[1] ;
单位： [1]Key Laboratory for Experimental Teratology of Ministry of Education and Department of Immunology, School of Basic Medical Sciences, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, P. R. China. [2]GI Cancer Research Institute,Tongji Hospital,Huazhong University of Science and Technology,Wuhan,Hubei,430074,P. R. China. [3]Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Disease, Department of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, 524001, P. R. China. [4]Shenzhen Research Institute of Shandong University, Shenzhen, 518057, P. R. China. [5]Advanced Medical Research Institute, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, P. R. China. [6]Central Laboratory, Tongji University School of Medicine, Tongji University, Shanghai, 200072, P. R. China. [7]Key Laboratory for Experimental Teratology of Ministry of Education and Department of Cell Biology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, P. R. China. [8]Department of Physiology, School of Basic Medical Sciences, Shandong University, Jinan, 250012, P. R. China. [9]State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, 200031, P. R. China. [10]Key Laboratory for Experimental Teratology of Ministry of Education and Department of Histology and Embryology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, P. R. China.
出处：
DOI： 10.1002/advs.202310065
ISSN：

摘要：
According to the latest evidence, the microbial metabolite Urolithin A (UA), known for its role in promoting cellular health, modulates CD8+ T cell-mediated antitumor activity. However, the direct target protein of UA and its underlying mechanism remains unclear. Here, this research identifies ERK1/2 as the specific target crucial for UA-mediated CD8+ T cell activation. Even at low doses, UA markedly enhances the persistence and effector functions of primary CD8+ cytotoxic T lymphocytes (CTLs) and human chimeric antigen receptor (CAR) T cells both in vitro and in vivo. Mechanistically, UA interacts directly with ERK1/2 kinases, enhancing their activation and subsequently facilitating T cell activation by engaging ULK1. The UA-ERK1/2-ULK1 axis promotes autophagic flux in CD8+ CTLs, enhancing cellular metabolism and maintaining reactive oxygen species (ROS) levels, as evidenced by increased oxygen consumption and extracellular acidification rates. UA-treated CD8+ CTLs also display elevated ATP levels and enhanced spare respiratory capacity. Overall, UA activates ERK1/2, inducing autophagy and metabolic adaptation, showcasing its potential in tumor immunotherapy and interventions for diseases involving ERKs.© 2024 The Authors. Advanced Science published by Wiley-VCH GmbH.

基金：
National key R&D program (grant 2021YFC2300603 to C.M.; 2022YFA1105303 to G.W.), National Natural Science Foundation of China (Key program 81830017, 82230056 to C.M.; grant 31600714 to C.L.; grant 82271878 to L.G.; grant 81922053, 82330084 to G.W.; grant 32270800 to W.W.), Taishan Scholarship (grant No. tspd20181201 to C.M.), Major Basic Research Project of Shandong Natural Science Foundation (grant ZR2020ZD12 to C.M.), Young Elite Scientist Sponsorship Program by Cast (grant YESS20160077 to C.L.), National Postdoctoral Program for Innovative Talents (grant BX201700147 to C.L.), Young Scholars Program of Shandong University (to C.L.), Cutting Edge Development Fund of Advanced Medical Research Institute (to X.L.), Shandong Excellent Young Scientists Fund Program (Overseas) (grant 2022HWYQ-028 to W.W.), Shandong Provincial Natural Science Foundation (grant ZR2022MC012 to W.W.), and Guangdong Basic and Applied Basic Research Foundation (grant 2021A1515110965 to W.W.)
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外文
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中科院(CAS)分区：
出版当年[2023]版：
大类 | 1 区 材料科学
小类 | 1 区 化学：综合 1 区 材料科学：综合 2 区 纳米科技
最新[2025]版：
大类 | 1 区 综合性期刊
小类 | 1 区 化学：综合 1 区 材料科学：综合 1 区 纳米科技
JCR分区：
出版当年[2022]版：
Q1 CHEMISTRY, MULTIDISCIPLINARY Q1 MATERIALS SCIENCE, MULTIDISCIPLINARY Q1 NANOSCIENCE & NANOTECHNOLOGY
最新[2023]版：
Q1 CHEMISTRY, MULTIDISCIPLINARY Q1 MATERIALS SCIENCE, MULTIDISCIPLINARY Q1 NANOSCIENCE & NANOTECHNOLOGY

影响因子： 最新[2023版] 最新五年平均 出版当年[2022版] 出版当年五年平均 出版前一年[2021版] 出版后一年[2023版]

第一作者：
第一作者单位： [1]Key Laboratory for Experimental Teratology of Ministry of Education and Department of Immunology, School of Basic Medical Sciences, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, P. R. China.
通讯作者：
推荐引用方式(GB/T 7714)：
Ma Shuaiya,Wu Qi,Wu Wenxian,et al.Urolithin A Hijacks ERK1/2-ULK1 Cascade to Improve CD8+ T Cell Fitness for Antitumor Immunity[J].ADVANCED SCIENCE.2024,e2310065.doi:10.1002/advs.202310065.
APA：
Ma Shuaiya,Wu Qi,Wu Wenxian,Tian Ye,Zhang Jie...&Ma Chunhong.(2024).Urolithin A Hijacks ERK1/2-ULK1 Cascade to Improve CD8+ T Cell Fitness for Antitumor Immunity.ADVANCED SCIENCE,,
MLA：
Ma Shuaiya,et al."Urolithin A Hijacks ERK1/2-ULK1 Cascade to Improve CD8+ T Cell Fitness for Antitumor Immunity".ADVANCED SCIENCE .(2024):e2310065

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