The TNFα/TNFR2 axis mediates natural killer cell proliferation by promoting aerobic glycolysis.
Glycolysis
Murine cytomegalovirus
Natural killer cells
Proliferation
TNFR2
TNFα
Journal
Cellular & molecular immunology
ISSN: 2042-0226
Titre abrégé: Cell Mol Immunol
Pays: China
ID NLM: 101242872
Informations de publication
Date de publication:
10 2023
10 2023
Historique:
received:
10
12
2022
accepted:
20
07
2023
revised:
29
06
2023
medline:
2
10
2023
pubmed:
9
8
2023
entrez:
8
8
2023
Statut:
ppublish
Résumé
Natural killer (NK) cells are predominant innate lymphocytes that initiate the early immune response during infection. NK cells undergo a metabolic switch to fuel augmented proliferation and activation following infection. Tumor necrosis factor-alpha (TNFα) is a well-known inflammatory cytokine that enhances NK cell function; however, the mechanism underlying NK cell proliferation in response to TNFα is not well established. Here, we demonstrated that upon infection/inflammation, NK cells upregulate the expression of TNF receptor 2 (TNFR2), which is associated with increased proliferation, metabolic activity, and effector function. Notably, IL-18 can induce TNFR2 expression in NK cells, augmenting their sensitivity toward TNFα. Mechanistically, TNFα-TNFR2 signaling upregulates the expression of CD25 (IL-2Rα) and nutrient transporters in NK cells, leading to a metabolic switch toward aerobic glycolysis. Transcriptomic analysis revealed significantly reduced expression levels of genes involved in cellular metabolism and proliferation in NK cells from TNFR2 KO mice. Accordingly, our data affirmed that genetic ablation of TNFR2 curtails CD25 upregulation and TNFα-induced glycolysis, leading to impaired NK cell proliferation and antiviral function during MCMV infection in vivo. Collectively, our results delineate the crucial role of the TNFα-TNFR2 axis in NK cell proliferation, glycolysis, and effector function.
Identifiants
pubmed: 37553427
doi: 10.1038/s41423-023-01071-4
pii: 10.1038/s41423-023-01071-4
pmc: PMC10541863
doi:
Substances chimiques
Receptors, Tumor Necrosis Factor, Type II
0
Tumor Necrosis Factor-alpha
0
Cytokines
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1140-1155Informations de copyright
© 2023. The Author(s).
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