Evidence map›Paper›PMID 33782423›Full record

ArticleScientific reports2021

STAT3 governs the HIF-1α response in IL-15 primed human NK cells.

Anna Coulibaly, Sonia Y Velásquez, Nina Kassner, Jutta Schulte, Maria Vittoria Barbarossa, Holger A Lindner

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

Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.1field-weighted citation impact, top 25% 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

17 citing papers in PubMed, 21 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

6 authors at 1 institution in 1 country.

Anna CoulibalyDepartment of Anesthesiology and Surgical Intensive Care Medicine, University Medical Center Mannheim, Mannheim Institute for Innate Immunoscience (MI3), Medical Faculty Mannheim, Heidelberg University, 68167, Mannheim, Germany.
Sonia Y VelásquezDepartment of Anesthesiology and Surgical Intensive Care Medicine, University Medical Center Mannheim, Mannheim Institute for Innate Immunoscience (MI3), Medical Faculty Mannheim, Heidelberg University, 68167, Mannheim, Germany.
Nina KassnerDepartment of Anesthesiology and Surgical Intensive Care Medicine, University Medical Center Mannheim, Mannheim Institute for Innate Immunoscience (MI3), Medical Faculty Mannheim, Heidelberg University, 68167, Mannheim, Germany.
Jutta SchulteDepartment of Anesthesiology and Surgical Intensive Care Medicine, University Medical Center Mannheim, Mannheim Institute for Innate Immunoscience (MI3), Medical Faculty Mannheim, Heidelberg University, 68167, Mannheim, Germany.
Maria Vittoria BarbarossaInterdisciplinary Center for Scientific Computing, Heidelberg University, 69120, Heidelberg, Germany.
Holger A LindnerDepartment of Anesthesiology and Surgical Intensive Care Medicine, University Medical Center Mannheim, Mannheim Institute for Innate Immunoscience (MI3), Medical Faculty Mannheim, Heidelberg University, 68167, Mannheim, Germany. Holger.Lindner@medma.uni-heidelberg.de.ORCID https://orcid.org/0000-0002-6679-4355
Heidelberg University · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Natural killer (NK) cells mediate innate host defense against microbial infection and cancer. Hypoxia and low glucose are characteristic for these tissue lesions but do not affect early interferon (IFN) γ and CC chemokine release by interleukin 15 (IL-15) primed human NK cells in vitro. Hypoxia inducible factor 1α (HIF-1α) mediates cellular adaption to hypoxia. Its production is supported by mechanistic target of rapamycin complex 1 (mTORC1) and signal transducer and activator of transcription 3 (STAT3). We used chemical inhibition to probe the importance of mTORC1 and STAT3 for the hypoxia response and of STAT3 for the cytokine response in isolated and IL-15 primed human NK cells. Cellular responses were assayed by magnetic bead array, RT-PCR, western blotting, flow cytometry, and metabolic flux analysis. STAT3 but not mTORC1 activation was essential for HIF-1α accumulation, glycolysis, and oxygen consumption. In both primed normoxic and hypoxic NK cells, STAT3 inhibition reduced the secretion of CCL3, CCL4 and CCL5, and it interfered with IL-12/IL-18 stimulated IFNγ production, but it did not affect cytotoxic granule degranulation up on target cell contact. We conclude that IL-15 priming promotes the HIF-1α dependent hypoxia response and the early cytokine response in NK cells predominantly through STAT3 signaling.

Indexed as

Cell DegranulationCell HypoxiaFlow CytometryGlycolysisHumansHypoxia-Inducible Factor 1, alpha SubunitImmunophenotypingInterleukin-15K562 CellsKiller Cells, NaturalMechanistic Target of Rapamycin Complex 1PhosphorylationSTAT3 Transcription FactorHIF1A protein, humanHypoxia-Inducible Factor 1, alpha SubunitIL15 protein, humanInterleukin-15Mechanistic Target of Rapamycin Complex 1STAT3 protein, humanSTAT3 Transcription Factor

Identifiers

PMID33782423
PMCPMC8007797
OpenAlexW3147560255

What OpenQuestion holds

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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.