Glycolysis and Oxidative Phosphorylation Play Critical Roles in Natural Killer Cell Receptor-Mediated Natural Killer Cell Functions
Natural killer (NK) cells are innate lymphocytes that directly kill tumor and pathogen-infected cells upon activation by cytokines and NK cell receptors (NKRs) without previous sensitization. It is known that cell metabolism affects the differentiation and effector functions of immune cells. For ins...
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Frontiers Media S.A.
2020-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2020.00202/full |
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| author | Zixi Wang Zixi Wang Di Guan Di Guan Shu Wang Louis Yi Ann Chai Louis Yi Ann Chai Shengli Xu Shengli Xu Kong-Peng Lam Kong-Peng Lam |
| author_facet | Zixi Wang Zixi Wang Di Guan Di Guan Shu Wang Louis Yi Ann Chai Louis Yi Ann Chai Shengli Xu Shengli Xu Kong-Peng Lam Kong-Peng Lam |
| author_sort | Zixi Wang |
| collection | DOAJ |
| description | Natural killer (NK) cells are innate lymphocytes that directly kill tumor and pathogen-infected cells upon activation by cytokines and NK cell receptors (NKRs) without previous sensitization. It is known that cell metabolism affects the differentiation and effector functions of immune cells. For instance, interleukin−2 and interleukin−15 treatment increases glycolysis and oxidative phosphorylation (OXPHOS) in NK cells to support their effector functions. However, little is known about the metabolic reprogramming of human NK cells upon their activation by NKRs. In this study, we investigated the metabolism of NK cells stimulated via NKRs. We found that NK cells upregulated glycolysis and OXPHOS in response to anti-CD16 antibody or NKG2D ligand engagement. Inhibition of either glycolysis or OXPHOS impaired NK cell production of interferon-γ. Interestingly, inhibition of glycolysis but not OXPHOS decreased NK cell killing and dampened NK cell degranulation and Fas ligand expression, suggesting that glycolysis is more critical for NKR-activated cell cytotoxicity. Thus, our study provides insight into understanding the metabolic requirements underlying different effector functions of human NK cells. |
| first_indexed | 2024-12-11T11:35:30Z |
| format | Article |
| id | doaj.art-cabffd486c1f4ec5b4016ea05d1d5ced |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-11T11:35:30Z |
| publishDate | 2020-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-cabffd486c1f4ec5b4016ea05d1d5ced2022-12-22T01:08:46ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-02-011110.3389/fimmu.2020.00202503939Glycolysis and Oxidative Phosphorylation Play Critical Roles in Natural Killer Cell Receptor-Mediated Natural Killer Cell FunctionsZixi Wang0Zixi Wang1Di Guan2Di Guan3Shu Wang4Louis Yi Ann Chai5Louis Yi Ann Chai6Shengli Xu7Shengli Xu8Kong-Peng Lam9Kong-Peng Lam10Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, SingaporeBioprocessing Technology Institute, Agency for Science, Technology and Research, Singapore, SingaporeBioprocessing Technology Institute, Agency for Science, Technology and Research, Singapore, SingaporeNUS Graduate School for Integrative Sciences & Engineering (NGS), National University of Singapore, Singapore, SingaporeDepartment of Biological Sciences, National University of Singapore, Singapore, SingaporeDivision of Infectious Diseases, University Medicine Cluster, National University Health System, Singapore, SingaporeDepartment of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, SingaporeBioprocessing Technology Institute, Agency for Science, Technology and Research, Singapore, SingaporeDepartment of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, SingaporeDepartment of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, SingaporeBioprocessing Technology Institute, Agency for Science, Technology and Research, Singapore, SingaporeNatural killer (NK) cells are innate lymphocytes that directly kill tumor and pathogen-infected cells upon activation by cytokines and NK cell receptors (NKRs) without previous sensitization. It is known that cell metabolism affects the differentiation and effector functions of immune cells. For instance, interleukin−2 and interleukin−15 treatment increases glycolysis and oxidative phosphorylation (OXPHOS) in NK cells to support their effector functions. However, little is known about the metabolic reprogramming of human NK cells upon their activation by NKRs. In this study, we investigated the metabolism of NK cells stimulated via NKRs. We found that NK cells upregulated glycolysis and OXPHOS in response to anti-CD16 antibody or NKG2D ligand engagement. Inhibition of either glycolysis or OXPHOS impaired NK cell production of interferon-γ. Interestingly, inhibition of glycolysis but not OXPHOS decreased NK cell killing and dampened NK cell degranulation and Fas ligand expression, suggesting that glycolysis is more critical for NKR-activated cell cytotoxicity. Thus, our study provides insight into understanding the metabolic requirements underlying different effector functions of human NK cells.https://www.frontiersin.org/article/10.3389/fimmu.2020.00202/fullnatural killer cellsanti-tumorcell metabolismglycolysisCD16NKG2D |
| spellingShingle | Zixi Wang Zixi Wang Di Guan Di Guan Shu Wang Louis Yi Ann Chai Louis Yi Ann Chai Shengli Xu Shengli Xu Kong-Peng Lam Kong-Peng Lam Glycolysis and Oxidative Phosphorylation Play Critical Roles in Natural Killer Cell Receptor-Mediated Natural Killer Cell Functions Frontiers in Immunology natural killer cells anti-tumor cell metabolism glycolysis CD16 NKG2D |
| title | Glycolysis and Oxidative Phosphorylation Play Critical Roles in Natural Killer Cell Receptor-Mediated Natural Killer Cell Functions |
| title_full | Glycolysis and Oxidative Phosphorylation Play Critical Roles in Natural Killer Cell Receptor-Mediated Natural Killer Cell Functions |
| title_fullStr | Glycolysis and Oxidative Phosphorylation Play Critical Roles in Natural Killer Cell Receptor-Mediated Natural Killer Cell Functions |
| title_full_unstemmed | Glycolysis and Oxidative Phosphorylation Play Critical Roles in Natural Killer Cell Receptor-Mediated Natural Killer Cell Functions |
| title_short | Glycolysis and Oxidative Phosphorylation Play Critical Roles in Natural Killer Cell Receptor-Mediated Natural Killer Cell Functions |
| title_sort | glycolysis and oxidative phosphorylation play critical roles in natural killer cell receptor mediated natural killer cell functions |
| topic | natural killer cells anti-tumor cell metabolism glycolysis CD16 NKG2D |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2020.00202/full |
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