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

Result code in 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>

Alternative codes found

RIV/00216224:14110/25:00143817 RIV/00216208:11310/25:10505557 RIV/00023736:_____/25:00013832

Result on the web

<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>

Result language

angličtina

Original language name

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

Original language description

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.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30102 - Immunology

Project

<a href="/en/project/NU22-08-00287" target="_blank" >NU22-08-00287: Natural Killer cell based adoptive cellular immunotherapy of hemato-oncology disorders.</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2025

Confidentiality

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

Name of the periodical

Journal of Inflammation-London

ISSN

1476-9255

e-ISSN

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Volume of the periodical

22

Issue of the periodical within the volume

1

Country of publishing house

GB - UNITED KINGDOM

Number of pages

13

Pages from-to

nestránkováno

UT code for WoS article

001594134700002

EID of the result in the Scopus database

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