Evidence map›Paper›PMID 37553427›Full record

ArticleCellular & molecular immunology2023

The TNFα/TNFR2 axis mediates natural killer cell proliferation by promoting aerobic glycolysis.

Abrar Ul Haq Khan, Alaa Kassim Ali, Bryan Marr, Donghyeon Jo, Simin Ahmadvand, Claire Fong-McMaster, Saeedah Musaed Almutairi, Lisheng Wang, Subash Sad, Mary-Ellen Harper and 1 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cellular & molecular immunology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed
10.7field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

39 citing papers in PubMed, 65 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 1 institution in 3 countries.

Abrar Ul Haq KhanDepartment of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada.
Alaa Kassim AliDepartment of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada.
Bryan MarrDepartment of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada.
Donghyeon JoDepartment of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada.
Simin AhmadvandDepartment of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada.
Claire Fong-McMasterDepartment of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada.
Saeedah Musaed AlmutairiDepartment of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada.
Lisheng WangDepartment of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada.
Subash SadDepartment of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada.ORCID http://orcid.org/0000-0002-2462-7137
Mary-Ellen HarperDepartment of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada.
Seung-Hwan LeeDepartment of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada. seunglee@uottawa.ca.
University of Ottawa · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

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.

Indexed as

Receptors, Tumor Necrosis Factor, Type IITumor Necrosis Factor-alphaAnimalsCell ProliferationCytokinesKiller Cells, NaturalMiceCytokinesReceptors, Tumor Necrosis Factor, Type IITumor Necrosis Factor-alphaGlycolysisMurine cytomegalovirusNatural killer cellsProliferationTNFR2TNFα

Identifiers

PMID37553427
PMCPMC10541863
OpenAlexW4385684132

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.