IL-10 Enhances Human Natural Killer Cell Effector Functions via Metabolic Reprogramming Regulated by mTORC1 Signaling

Cell metabolism plays a pivotal role in regulating the effector functions of immune cells. Stimulatory cytokines, such as interleukin (IL)-2 or IL-12 and IL-15, activate glycolysis and oxidative phosphorylation in natural killer (NK) cells to support their enhanced effector functions. IL-10, a pleio...

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Published inFrontiers in immunology Vol. 12; p. 619195
Main Authors Wang, Zixi, Guan, Di, Huo, Jianxin, Biswas, Subhra K, Huang, Yuhan, Yang, Yuansheng, Xu, Shengli, Lam, Kong-Peng
Format Journal Article
LanguageEnglish
Published Switzerland Frontiers Media S.A 23.02.2021
Subjects
cytotoxicity
IFN-γ
IL-10
Immunology
metabolism
mTOR
NK cell
mTOR
IFN-γ
metabolism
IL-10
cytotoxicity
NK cell
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Abstract Cell metabolism plays a pivotal role in regulating the effector functions of immune cells. Stimulatory cytokines, such as interleukin (IL)-2 or IL-12 and IL-15, activate glycolysis and oxidative phosphorylation in natural killer (NK) cells to support their enhanced effector functions. IL-10, a pleiotropic cytokine, is known to suppress macrophage activation but stimulate NK cells. However, it remains unclear if IL-10 has an effect on the metabolism of human NK cells and if so, what metabolic mechanisms are affected, and how these metabolic changes are regulated and contribute to the effector functions of NK cells. In this study, we demonstrate that IL-10 upregulates both glycolysis and oxidative phosphorylation in human NK cells, and these metabolic changes are crucial for the enhanced effector functions of NK cells. Mechanistically, we unravel that IL-10 activates the mammalian target of rapamycin complex 1 (mTORC1) to regulate metabolic reprogramming in human NK cells.
AbstractList Cell metabolism plays a pivotal role in regulating the effector functions of immune cells. Stimulatory cytokines, such as interleukin (IL)-2 or IL-12 and IL-15, activate glycolysis and oxidative phosphorylation in natural killer (NK) cells to support their enhanced effector functions. IL-10, a pleiotropic cytokine, is known to suppress macrophage activation but stimulate NK cells. However, it remains unclear if IL-10 has an effect on the metabolism of human NK cells and if so, what metabolic mechanisms are affected, and how these metabolic changes are regulated and contribute to the effector functions of NK cells. In this study, we demonstrate that IL-10 upregulates both glycolysis and oxidative phosphorylation in human NK cells, and these metabolic changes are crucial for the enhanced effector functions of NK cells. Mechanistically, we unravel that IL-10 activates the mammalian target of rapamycin complex 1 (mTORC1) to regulate metabolic reprogramming in human NK cells.
Author Guan, Di
Biswas, Subhra K
Huang, Yuhan
Xu, Shengli
Yang, Yuansheng
Huo, Jianxin
Wang, Zixi
Lam, Kong-Peng
AuthorAffiliation 4 Singapore Immunology Network (SIgN), ASTAR (Agency for Science, Technology and Research) , Singapore , Singapore
1 Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore , Singapore , Singapore
2 Bioprocessing Technology Institute, ASTAR (Agency for Science, Technology and Research) , Singapore , Singapore
3 NUS Graduate School for Integrative Sciences & Engineering (NGS), National University of Singapore , Singapore , Singapore
5 Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore , Singapore , Singapore
AuthorAffiliation_xml – name: 1 Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore , Singapore , Singapore
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– name: 4 Singapore Immunology Network (SIgN), ASTAR (Agency for Science, Technology and Research) , Singapore , Singapore
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Copyright Copyright © 2021 Wang, Guan, Huo, Biswas, Huang, Yang, Xu and Lam.
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Keywords mTOR
IFN-γ
metabolism
IL-10
cytotoxicity
NK cell
Language English
License Copyright © 2021 Wang, Guan, Huo, Biswas, Huang, Yang, Xu and Lam.
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Reviewed by: Norberto Walter Zwirner, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina; Bart Everts, Leiden University Medical Center, Netherlands
Edited by: Eleanor Riley, University of Edinburgh, United Kingdom
This article was submitted to NK and Innate Lymphoid Cell Biology, a section of the journal Frontiers in Immunology
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Snippet Cell metabolism plays a pivotal role in regulating the effector functions of immune cells. Stimulatory cytokines, such as interleukin (IL)-2 or IL-12 and...
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SubjectTerms cytotoxicity
IFN-γ
IL-10
Immunology
metabolism
mTOR
NK cell
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Title IL-10 Enhances Human Natural Killer Cell Effector Functions via Metabolic Reprogramming Regulated by mTORC1 Signaling
URI https://www.ncbi.nlm.nih.gov/pubmed/33708210
https://search.proquest.com/docview/2501254694
https://pubmed.ncbi.nlm.nih.gov/PMC7940510
https://doaj.org/article/f9f6d1be24ff46a7acb99d102b7e248c
Volume 12
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