Evidence map›Paper›PMID 39772395›Full record

ArticleCell reports2025

Metabolic reprogramming of macrophages by PKM2 promotes IL-10 production via adenosine.

Juliana Escher Toller-Kawahisa, Paula Ramos Viacava, Eva Margareta Palsson-McDermott, Daniele Carvalho Nascimento, Mariana Patricia Cervantes-Silva, Shane Myles O'Carroll, Alessia Zotta, Luis Eduardo Alves Damasceno, Gabriel Azevedo Públio, Pedro Forti and 9 more

Abstract read
In one paragraph

Article in Cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

27 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Hyperprogressive disease in carcinoma induced by immune checkpoint inhibitor therapy: a systematic review.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Pooled it
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  14. Effect of PKM2 onFrontiers in cellular and infection microbiology · 2026
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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

19 authors.

Juliana Escher Toller-KawahisaDepartment of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil; Center for Research in Inflammatory Diseases, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil; School of Biochemistry and Immunology, Trinity Biomedical Science Institute, Trinity College Dublin, Dublin, Ireland.
Paula Ramos ViacavaDepartment of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil; Center for Research in Inflammatory Diseases, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil.
Eva Margareta Palsson-McDermottSchool of Biochemistry and Immunology, Trinity Biomedical Science Institute, Trinity College Dublin, Dublin, Ireland.
Daniele Carvalho NascimentoDepartment of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil; Center for Research in Inflammatory Diseases, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil.
Mariana Patricia Cervantes-SilvaSchool of Pharmacy and Biomolecular Sciences and Tissue Engineering Research Group, Royal College of Surgeons in Ireland, Dublin, Ireland.
Shane Myles O'CarrollSchool of Biochemistry and Immunology, Trinity Biomedical Science Institute, Trinity College Dublin, Dublin, Ireland.
Alessia ZottaSchool of Biochemistry and Immunology, Trinity Biomedical Science Institute, Trinity College Dublin, Dublin, Ireland.
Luis Eduardo Alves DamascenoDepartment of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil; Center for Research in Inflammatory Diseases, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil.
Gabriel Azevedo PúblioDepartment of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil; Center for Research in Inflammatory Diseases, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil.
Pedro FortiDepartment of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil; Center for Research in Inflammatory Diseases, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil.
João Paulo Mesquita LuizDepartment of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil; Center for Research in Inflammatory Diseases, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil.
Bruno Marcel Silva de MeloDepartment of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil; Center for Research in Inflammatory Diseases, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil.
Timna Varela MartinsDepartment of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil; Center for Research in Inflammatory Diseases, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil.
Vitor Marcel FaçaDepartment of Biochemistry and Immunology, Ribeirao Preto Medical School, University of São Paulo, Ribeirao Preto, Brazil.
Annie CurtisSchool of Pharmacy and Biomolecular Sciences and Tissue Engineering Research Group, Royal College of Surgeons in Ireland, Dublin, Ireland.
Thiago Mattar CunhaDepartment of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil; Center for Research in Inflammatory Diseases, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil.
Fernando de Queiroz CunhaDepartment of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil; Center for Research in Inflammatory Diseases, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil.
Luke Anthony John O'NeillSchool of Biochemistry and Immunology, Trinity Biomedical Science Institute, Trinity College Dublin, Dublin, Ireland. Electronic address: laoneill@tcd.ie.
José Carlos Alves-FilhoDepartment of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil; Center for Research in Inflammatory Diseases, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil. Electronic address: jcafilho@usp.br.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Macrophages play a crucial role in immune responses and undergo metabolic reprogramming to fulfill their functions. The tetramerization of the glycolytic enzyme pyruvate kinase M2 (PKM2) induces the production of the anti-inflammatory cytokine interleukin (IL)-10 in vivo, but the underlying mechanism remains elusive. Here, we report that PKM2 activation with the pharmacological agent TEPP-46 increases IL-10 production in LPS-activated macrophages by metabolic reprogramming, leading to the production and release of ATP from glycolysis. The effect of TEPP-46 is abolished in PKM2-deficient macrophages. Extracellular ATP is converted into adenosine by ectonucleotidases that activate adenosine receptor A2a (A2aR) to enhance IL-10 production. Interestingly, IL-10 production induced by PKM2 activation is associated with improved mitochondrial health. Our results identify adenosine derived from glycolytic ATP as a driver of IL-10 production, highlighting the role of tetrameric PKM2 in regulating glycolysis to promote IL-10 production.

Indexed as

AdenosineInterleukin-10MacrophagesPyruvate KinaseAdenosine TriphosphateAnimalsGlycolysisHumansLipopolysaccharidesMetabolic ReprogrammingMiceMice, Inbred C57BLMitochondriaReceptor, Adenosine A2AAdenosineAdenosine TriphosphateIL10 protein, mouseInterleukin-10LipopolysaccharidesPkm protein, mousePyruvate KinaseReceptor, Adenosine A2AadenosineCP: ImmunologyCP: MetabolismIL-10macrophagemitochondria dynamicsPKM2

Identifiers

PMID39772395
PMCPMC11781862

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

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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.