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Title: | THE ROLE OF NK CELL METABOLISM IN NK CELL ACTIVATION AND FUNCTION | Authors: | WANG ZIXI | Keywords: | metabolism, glycolysis, OXPHOS, natural killer cell, natural killer cell receptor, NK cell function | Issue Date: | 15-Jan-2020 | Citation: | WANG ZIXI (2020-01-15). THE ROLE OF NK CELL METABOLISM IN NK CELL ACTIVATION AND FUNCTION. ScholarBank@NUS Repository. | Abstract: | Natural killer (NK) cell activation is modulated by cytokines and NK cell receptors (NKRs). It has been found that NK cells stimulated by activating cytokines (e.g. interleukin-15) increase glycolysis and oxidative phosphorylation (OXPHOS) to support their effector functions. However, little is known about the metabolic reprogramming of human NK cells upon NKR activation. In this study, we investigated the metabolic changes of NK cells activated by NKRs. We found that NK cells upregulated glycolysis and OXPHOS in response to anti-CD16 antibody and NKG2D ligand engagement. We further investigated the impact of glycolysis and OXPHOS on NK cell effector functions. We found that inhibition of either glycolysis or OXPHOS impaired NK cell production of interferon-γ. Interestingly, inhibiting glycolysis but not OXPHOS decreased the cytotoxicity of expanded NK cells by supressing degranulation and Fas ligand expression. Thus, our study provides insight into understanding the metabolic requirements of NKR-activated human NK cells. | URI: | https://scholarbank.nus.edu.sg/handle/10635/176933 |
Appears in Collections: | Ph.D Theses (Open) |
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