https://scholars.lib.ntu.edu.tw/handle/123456789/596770
標題: | NK cell receptor and ligand composition influences the clearance of SARS-CoV-2 | 作者: | Hsieh, Wan-Chen Lai, En-Yu Liu, Yu-Ting Wang, Yi-Fu Tzeng, Yi-Shiuan Cui, Lu Lai, Yun-Ju Huang, Hsiang-Chi Huang, Jia-Hsin Ni, Hung-Chih Tsai, Dong-Yan Liang, Jian-Jong Liao, Chun-Che Lu, Ya-Ting Jiang, Laurence Liu, Ming-Tsan JANN-TAY WANG SUI-YUAN CHANG Chen, Chung-Yu HSING-CHEN TSAI Chang, Yao-Ming Wernig, Gerlinde Li, Chia-Wei Lin, Kuo-I Lin, Yi-Ling Tsai, Huai-Kuang Huang, Yen-Tsung Chen, Shih-Yu |
關鍵字: | COVID-19; NK cells | 公開日期: | 2021 | 出版社: | AMER SOC CLINICAL INVESTIGATION INC | 卷: | 131 | 期: | 21 | 來源出版物: | The Journal of Clinical Investigation | 摘要: | To explore how the immune system controls clearance of SARS-CoV-2, we used a single-cell, mass cytometry-based proteomics platform to profile the immune systems of 21 patients who had recovered from SARS-CoV-2 infection without need for admission to an intensive care unit or for mechanical ventilation. We focused on receptors involved in interactions between immune cells and virus-infected cells. We found that the diversity of receptor repertoires on natural killer (NK) cells was negatively correlated with the viral clearance rate. In addition, NK subsets expressing the receptor DNAM1 were increased in patients who more rapidly recovered from infection. Ex vivo functional studies revealed that NK subpopulations with high DNAM1 expression had cytolytic activities in response to target cell stimulation. We also found that SARS-CoV-2 infection induced the expression of CD155 and nectin-4, ligands of DNAM1 and its paired coinhibitory receptor TIGIT, which counterbalanced the cytolytic activities of NK cells. Collectively, our results link the cytolytic immune responses of NK cells to the clearance of SARS-CoV-2 and show that the DNAM1 pathway modulates host-pathogen interactions during SARS-CoV-2 infection. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/596770 | ISSN: | 1558-8238 | DOI: | 10.1172/JCI146408 | SDG/關鍵字: | natural killer cell receptor; nectin; CD226 antigen; cell adhesion molecule; immunoglobulin receptor; ligand; natural killer cell lectin like receptor subfamily D; natural killer cell receptor; nectin4 protein, human; poliovirus receptor; T lymphocyte antigen; TIGIT protein, human; virus receptor; adult; aged; Article; artificial ventilation; clinical article; controlled study; coronavirus disease 2019; cytolysis; ex vivo study; female; HEK293T cell line; human; human cell; human tissue; LCL 721.221 cell line; male; mass cytometry; natural killer cell; natural killer cell mediated cytotoxicity; peripheral blood mononuclear cell; protein expression; protein expression level; proteomics; Severe acute respiratory syndrome coronavirus 2; target cell; viral clearance; virus immunity; adolescent; animal; cohort analysis; cytotoxicity; immunology; immunophenotyping; in vitro study; middle aged; mouse; pandemic; SCID mouse; virology; virus load; xenograft; young adult; Adolescent; Adult; Aged; Animals; Antigens, Differentiation, T-Lymphocyte; Cell Adhesion Molecules; Cohort Studies; COVID-19; Cytotoxicity, Immunologic; Female; Heterografts; Host Microbial Interactions; Humans; Immunophenotyping; In Vitro Techniques; Killer Cells, Natural; Ligands; Male; Mice; Mice, SCID; Middle Aged; NK Cell Lectin-Like Receptor Subfamily D; Pandemics; Receptors, Immunologic; Receptors, Natural Killer Cell; Receptors, Virus; SARS-CoV-2; Viral Load; Young Adult |
顯示於: | 毒理學研究所 |
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