Glutaminase activity maintains NK cell cytotoxicity through metabolic regulation of effector function

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00159816%3A_____%2F25%3A00082227" target="_blank" >RIV/00159816:_____/25:00082227 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216224:14110/25:00143817 RIV/00216208:11310/25:10505557

Výsledek na webu

<a href="https://link.springer.com/article/10.1186/s12950-025-00470-w" target="_blank" >https://link.springer.com/article/10.1186/s12950-025-00470-w</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1186/s12950-025-00470-w" target="_blank" >10.1186/s12950-025-00470-w</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Glutaminase activity maintains NK cell cytotoxicity through metabolic regulation of effector function

Popis výsledku v původním jazyce

BackgroundNatural killer (NK) cells are responsible for monitoring and eliminating malignant or virus-infected cells. To become activated, NK cells must upregulate oxidative phosphorylation and glycolysis to meet the high energetic demands associated with cytotoxic and effector functions. While glutamine can also fuel the tricarboxylic acid cycle through its conversion to alpha-ketoglutarate, the precise role of this pathway in NK-cell cytotoxic activity is unclear.ResultsTo investigate NK-cell dependency on glutamine, we selectively inhibited kidney-type glutaminase to prevent glutamine metabolism. We analysed the metabolism and cytotoxicity of expanded primary NK cells, treated or not with glutaminase inhibitor. Glutaminase inhibition significantly reduced oxidative phosphorylation and led to a significant decrease in NK cell cytotoxic function. Furthermore, glutaminase inhibition reduced protein synthesis in activated NK cells. Meanwhile, supplementation with alpha-ketoglutarate rescued both the metabolic and cytotoxic capacities of primary expanded NK cells.ConclusionsOur findings highlight the importance of glutaminase activity in supporting NK cell respiratory metabolism and cytotoxic function, and the need for caution when combining glutaminase inhibitors with NK cell-based therapies.

Název v anglickém jazyce

Glutaminase activity maintains NK cell cytotoxicity through metabolic regulation of effector function

Popis výsledku anglicky

BackgroundNatural killer (NK) cells are responsible for monitoring and eliminating malignant or virus-infected cells. To become activated, NK cells must upregulate oxidative phosphorylation and glycolysis to meet the high energetic demands associated with cytotoxic and effector functions. While glutamine can also fuel the tricarboxylic acid cycle through its conversion to alpha-ketoglutarate, the precise role of this pathway in NK-cell cytotoxic activity is unclear.ResultsTo investigate NK-cell dependency on glutamine, we selectively inhibited kidney-type glutaminase to prevent glutamine metabolism. We analysed the metabolism and cytotoxicity of expanded primary NK cells, treated or not with glutaminase inhibitor. Glutaminase inhibition significantly reduced oxidative phosphorylation and led to a significant decrease in NK cell cytotoxic function. Furthermore, glutaminase inhibition reduced protein synthesis in activated NK cells. Meanwhile, supplementation with alpha-ketoglutarate rescued both the metabolic and cytotoxic capacities of primary expanded NK cells.ConclusionsOur findings highlight the importance of glutaminase activity in supporting NK cell respiratory metabolism and cytotoxic function, and the need for caution when combining glutaminase inhibitors with NK cell-based therapies.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

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OECD FORD obor

30102 - Immunology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal of Inflammation-London

ISSN

1476-9255

e-ISSN

—

Svazek periodika

22

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

13

Strana od-do

nestránkováno

Kód UT WoS článku

001594134700002

EID výsledku v databázi Scopus

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