immunology; lymphocyte; cytotoxic lymphocyte; long non-coding RNA; viral infection
Abstract :
[en] The efficient induction and long-term persistence of pathogen-specific memory CD8 T cells are pivotal to rapidly curb the reinfection. Recent studies indicated that long-noncoding RNAs expression is highly cell- and stage-specific during T cell development and differentiation, suggesting their potential roles in T cell programs. However, the key lncRNAs playing crucial roles in memory CD8 T cell establishment remain to be clarified. Through CD8 T cell subsets profiling of lncRNAs, this study found a key lncRNA-Snhg1 with the conserved naivehi-effectorlo-memoryhi expression pattern in CD8 T cells of both mice and human, that can promote memory formation while impeding effector CD8 in acute viral infection. Further, Snhg1 was found interacting with the conserved vesicle trafficking protein Vps13D to promote IL-7Rα membrane location specifically. With the deep mechanism probing, the results show Snhg1-Vps13D regulated IL-7 signaling with its dual effects in memory CD8 generation, which not just because of the sustaining role of STAT5-BCL-2 axis for memory survival, but more through the STAT3-TCF1-Blimp1 axis for transcriptional launch program of memory differentiation. Moreover, we performed further study with finding a similar high-low-high expression pattern of human SNHG1/VPS13D/IL7R/TCF7 in CD8 T cell subsets from PBMC samples of the convalescent COVID-19 patients. The central role of Snhg1-Vps13D-IL-7R-TCF1 axis in memory CD8 establishment makes it a potential target for improving the vaccination effects to control the ongoing pandemic.
Zhang, Yanyan ; Institute of Immunology PLA, Third Military Medical University, Chongqing, China ; Institute of Hepatopancreatobiliary Surgery, Chongqing General Hospital, University of Chinese Academy of Sciences, Chongqing, China
Li, Baohua; Institute of Immunology PLA, Third Military Medical University, Chongqing, China
Bai, Qiang ; Université de Liège - ULiège > Département des sciences fonctionnelles (DSF) ; Institute of Immunology PLA, Third Military Medical University, Chongqing, China
Wang, Pengcheng; Institute of Immunology PLA, Third Military Medical University, Chongqing, China
Wei, Gang; Human Phenome Institute, Fudan University, Shanghai, China
Li, Zhirong; Institute of Immunology PLA, Third Military Medical University, Chongqing, China
Hu, Li; Institute of Immunology PLA, Third Military Medical University, Chongqing, China
Tian, Qin; Institute of Immunology PLA, Third Military Medical University, Chongqing, China
Zhou, Jing; Institute of Immunology PLA, Third Military Medical University, Chongqing, China
Huang, Qizhao; Institute of Immunology PLA, Third Military Medical University, Chongqing, China
Wang, Zhiming; Institute of Immunology PLA, Third Military Medical University, Chongqing, China
Yue, Shuai; Institute of Immunology PLA, Third Military Medical University, Chongqing, China
Wu, Jialin; Institute of Immunology PLA, Third Military Medical University, Chongqing, China
Yang, Liuqing ; Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, United States
Zhou, Xinyuan; Institute of Immunology PLA, Third Military Medical University, Chongqing, China
Jiang, Lubin; Institute Pasteur of Shanghai, Chinese Academy of Sciences (CAS), Shanghai, China
Ni, Ting; Human Phenome Institute, Fudan University, Shanghai, China
Ye, Lilin ; Institute of Immunology PLA, Third Military Medical University, Chongqing, China
Wu, Yuzhang; Institute of Immunology PLA, Third Military Medical University, Chongqing, China
NSCF - National Natural Science Foundation of China
Funding text :
This study was supported by grants from the National Natural Science Foundation of China (No. 31800763 to Y.Z.), Special Grant from Postdoctoral Science Foundation of China (No. 2020T130791 to Y.Z.) and the National Key Research and Development Plan of China (No. 2016YFA0502202 to L.Y). We thank Dr. Ting Ni (Fudan University) for the RNA sequencing. We thank Dr. Rafi Ahmed (Emory University) for P14 transgenic mice and retroviral vectors. And we thank Dr. Liuqing Yang (M.D. Anderson Cancer Centre) for the pGEX-3Z vector.
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