Themis suppresses the effector function of CD8^(+)T cells in acute viral infection

作     者：Jian Tang Xian Jia Jian Li Junchen Dong Jiayu Wang Wanyun Li Yuzhen Zhu Yanyan Hu Bowen Hou Chunjie Lin Yu Cong Tong Ren Changsheng Yan Hongying Yang Qian Lai Haiping Zheng Yuzhou Bao Namrata Gautam Hong-Rui Wang Bing Xu Xiao Lei Chen Qing Li Nicholas R.J.Gascoigne Guo Fu 

作者机构：State Key Laboratory of Cellular Stress BiologySchool of MedicineFaculty of Medicine and Life SciencesXiamen UniversityXiamenChina School of Life SciencesXiamen UniversityXiamenChina Immunology Translational Research ProgrammeYong Loo Lin School of MedicineNational University of SingaporeSingaporeSingapore Department of Microbiology and ImmunologyYong Loo Lin School of MedicineNational University of SingaporeSingaporeSingapore Department of HematologyThe First Affiliated Hospital and Institute of HematologySchool of MedicineXiamen UniversityXiamenChina Cancer Research Center of Xiamen UniversityXiamenChina 

出 版 物：《Cellular & Molecular Immunology》 (中国免疫学杂志（英文版）)

年 卷 期：2023年第20卷第5期

页      面：512-524页

核心收录：

学科分类：1001[医学-基础医学(可授医学、理学学位)] 100102[医学-免疫学] 10[医学] 

基　　金：the Core Facility of Biomedical Sciences,Xiamen University for Flow Cytometry Cell Sorting service.This study was supported by the National Natural Science Foundation of China(32070887) the Fundamental Research Funds for the Central Universities(20720220003)to G.F.Singapore Ministry of Education(MOE-000112) Singapore Ministry of Health's National Medical Research Council(MOH-000523)to N.RJ.Gascoigne.The Natural Science Foundation of Fujian Province(No.2019J01009)to Q.L.The National Natural Science Foundation of China(U1904206)to X.L.C.The funders had no role in the study design,data collection and analysis,decision to publish,or preparation of the manuscript 

主　　题：Themis Effector T cell CD8 T-cell differentiation Cytokine LCMV 

摘      要：CD8^(+)T cells play a central role in antiviral immune *** infection,naive CD8^(+)T cells differentiate into effector cells to eliminate virus-infected cells,and some of these effector cells further differentiate into memory cells to provide long-term protection after infection is *** extensively investigated,the underlying mechanisms of CD+T-cell differentiation remain incompletely *** is a T-cell-specific protein that plays critical roles in T-cell *** studies using Themis T-cell conditional knockout mice also demonstrated that Themis is required to promote mature CD8^(+)T-cell homeostasis,cytokine responsiveness,and antibacterial *** this study,we used LCMV Armstrong infection as a probe to explore the role of Themis in viral *** found that preexisting CD8^(+)T-cell homeostasis defects and cytokine hyporesponsiveness do not impair viral clearance in Themis T-cell conditional knockout *** analyses showed that in the primary immune response,Themis deficiency promoted the differentiation of CD8^(+)effector cells and increased their TNF and IFNy ***,Themis deficiency impaired memory precursor cell(MPEC)differentiation but promoted short-lived effector cell(SLEC)*** deficiency also enhanced effector cytokine production in memory CD8^(+)T cells while impairing central memory CD8^(+)T-cell ***,we found that Themis mediates PD-1 expression and its signaling in effector CD8^(+)T cells,which explains the elevated cytokine production in these cells when Themis is disrupted.