Glycolysis and Oxidative Phosphorylation Play Critical Roles in Natural Killer Cell Receptor-Mediated Natural Killer Cell Functions.

Frontiers in Immunology
Zixi WangKong-Peng Lam

Abstract

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.

References

Jan 1, 1989·Advances in Immunology·G Trinchieri
Jan 1, 1985·Annual Review of Immunology·P A Henkart
Nov 5, 2002·Nature Reviews. Cancer·Mark J SmythHideo Yagita
Dec 21, 2004·Molecular Immunology·Mark J SmythYoshihiro Hayakawa
Jun 27, 2006·Nature Reviews. Immunology·David H Raulet, Russell E Vance
Apr 23, 2009·Cancer Research·Hiroyuki FujisakiDario Campana
Jan 8, 2011·Science·Eric VivierSophie Ugolini
Aug 31, 2011·Proceedings of the National Academy of Sciences of the United States of America·Alice E DentonStephen J Turner
Mar 23, 2012·Nature Reviews. Immunology·Eric VivierLaurent Brossay
Apr 23, 2013·Immunity·Erika L Pearce, Edward J Pearce
Jun 11, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Alessandra SorianiAngela Santoni
Sep 28, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Raymond P DonnellyDavid K Finlay
Dec 31, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Francesca Alvarez-CalderonJames DeGregori
Jan 18, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Molly P KeppelMegan A Cooper
Feb 14, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sinéad E KeatingClair M Gardiner
Feb 18, 2016·Science Signaling·Sébastien VielThierry Walzer
Aug 11, 2018·The Journal of Allergy and Clinical Immunology·Jolie R SchaferDean A Lee
Jan 9, 2019·Frontiers in Immunology·Caroline PfeiferChristian Körner

❮ Previous
Next ❯

Citations

Aug 9, 2020·Molecular Cancer·Song-Yang WuZhi-Ming Shao
Feb 7, 2021·Molecular Cancer·Longzheng XiaQianjin Liao
May 8, 2021·Mucosal Immunology·Pablo C AlarconSenad Divanovic
May 16, 2021·Applied Microbiology and Biotechnology·Zhepei XieHaibo Cai
May 11, 2021·Analytical Sciences : the International Journal of the Japan Society for Analytical Chemistry·Kenta TanitoYoshiki Katayama

❮ Previous
Next ❯

Methods Mentioned

BETA
flow cytometry
PCR
ELISA
histone acetylation

Software Mentioned

GraphPad Prism

Related Concepts

Related Feeds

Allergy and Asthma

Allergy and asthma are inflammatory disorders that are triggered by the activation of an allergen-specific regulatory t cell. These t cells become activated when allergens are recognized by allergen-presenting cells. Here is the latest research on allergy and asthma.

Cancer Biology: Molecular Imaging

Molecular imaging enables noninvasive imaging of key molecules that are crucial to tumor biology. Discover the latest research in molecular imaging in cancer biology in this feed.

Cancer Metabolism

In order for cancer cells to maintain rapid, uncontrolled cell proliferation, they must acquire a source of energy. Cancer cells acquire metabolic energy from their surrounding environment and utilize the host cell nutrients to do so. Here is the latest research on cancer metabolism.