Evidence mapPaperPMID 37978290Full record

ArticleNature communications2023

Inflammatory macrophages reprogram to immunosuppression by reducing mitochondrial translation.

Marlies Cortés, Agnese Brischetto, M C Martinez-Campanario, Chiara Ninfali, Verónica Domínguez, Sara Fernández, Raquel Celis, Anna Esteve-Codina, Juan J Lozano, Julia Sidorova and 8 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed, 1 pooled it
10.5field-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

44 citing papers in PubMed, 1 synthesis or guideline pooled it, 64 citations in OpenAlex.

  1. Pooled it
  2. Role of ZEB1 in angiogenesis and therapeutic potential (Review).International journal of molecular medicine · 2026
    Review
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Review
  12. Article
  13. Review
  14. Article
  15. Article
  16. Macrophages: sentinels, warriors, and healers.Human molecular genetics · 2025
    Review
  17. Review
  18. Islet Tissue Macrophages in Immunity Homeostasis and Type 1 Diabetes.Clinical reviews in allergy & immunology · 2025
    Review
  19. Monocyte Involvement in the Pathogenesis of Myeloproliferative Neoplasms.International journal of molecular sciences · 2025
    Review
  20. Article
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

18 authors at 9 institutions in 3 countries.

Marlies CortésGroup of Gene Regulation in Stem Cells, Cell Plasticity, Differentiation, and Cancer, IDIBAPS, 08036, Barcelona, Spain. mcortesh@recerca.clinic.cat.ORCID http://orcid.org/0000-0002-9313-1194
Agnese Brischetto *Group of Gene Regulation in Stem Cells, Cell Plasticity, Differentiation, and Cancer, IDIBAPS, 08036, Barcelona, Spain.ORCID http://orcid.org/0000-0002-7056-8721
M C Martinez-Campanario *Group of Gene Regulation in Stem Cells, Cell Plasticity, Differentiation, and Cancer, IDIBAPS, 08036, Barcelona, Spain.ORCID http://orcid.org/0000-0002-2745-6505
Chiara NinfaliGroup of Gene Regulation in Stem Cells, Cell Plasticity, Differentiation, and Cancer, IDIBAPS, 08036, Barcelona, Spain.ORCID http://orcid.org/0000-0002-5745-6119
Verónica DomínguezNational Center of Biotechnology (CSIC-CNB) and Center for Molecular Biology Severo Ochoa (CSIC/UAM-CBMSO) Transgenesis Facility, Higher Research Council (CSIC) and Autonomous University of Madrid (UAM), Cantoblanco, 28049, Madrid, Spain.
Sara FernándezMedical Intensive Care Unit and Department of Internal Medicine, Hospital Clínic of Barcelona, Group of Muscle Research and Mitochondrial Function, IDIBAPS, and CIBERER, 08036, Barcelona, Spain.
Raquel CelisArthritis Unit, Dept. of Rheumathology, Hospital Clínic and IDIBAPS, 08036, Barcelona, Spain.
Anna Esteve-CodinaNational Center for Genomics Analysis (CNAG), 08028, Barcelona, Spain.
Juan J LozanoBiomedical Research Networking Centers in Digestive and Hepatic Diseases (CIBERehd), Carlos III Health Institute, 08036, Barcelona, Spain.
Julia SidorovaBiomedical Research Networking Centers in Digestive and Hepatic Diseases (CIBERehd), Carlos III Health Institute, 08036, Barcelona, Spain.
Gloria GarrabouMedical Intensive Care Unit and Department of Internal Medicine, Hospital Clínic of Barcelona, Group of Muscle Research and Mitochondrial Function, IDIBAPS, and CIBERER, 08036, Barcelona, Spain.
Anna-Maria SiegertMRC Metabolic Diseases Unit, University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, CB1 0QQ, UK.ORCID http://orcid.org/0000-0002-8694-5894
Carlos EnrichDepartment of Biomedicine, University of Barcelona School of Medicine and Health Sciences, 08036, Barcelona, Spain.
Belén PintadoNational Center of Biotechnology (CSIC-CNB) and Center for Molecular Biology Severo Ochoa (CSIC/UAM-CBMSO) Transgenesis Facility, Higher Research Council (CSIC) and Autonomous University of Madrid (UAM), Cantoblanco, 28049, Madrid, Spain.
Manuel Morales-RuizBiomedical Research Networking Centers in Digestive and Hepatic Diseases (CIBERehd), Carlos III Health Institute, 08036, Barcelona, Spain.ORCID http://orcid.org/0000-0002-9074-2272
Pedro CastroMedical Intensive Care Unit and Department of Internal Medicine, Hospital Clínic of Barcelona, Group of Muscle Research and Mitochondrial Function, IDIBAPS, and CIBERER, 08036, Barcelona, Spain.ORCID http://orcid.org/0000-0002-6118-8970
Juan D CañeteArthritis Unit, Dept. of Rheumathology, Hospital Clínic and IDIBAPS, 08036, Barcelona, Spain.
Antonio PostigoGroup of Gene Regulation in Stem Cells, Cell Plasticity, Differentiation, and Cancer, IDIBAPS, 08036, Barcelona, Spain. idib412@recerca.clinic.cat.ORCID http://orcid.org/0000-0003-4605-2634
Centre for Genomic Regulation · ESCentro de Investigación Biomédica en Red · ESInstituto de Salud Carlos III · ESCentro de Biología Molecular Severo Ochoa · ESHospital Clínic de Barcelona · ESCentro Nacional de Análisis Genómico · ESUniversitat de Barcelona · ESUniversity of Cambridge · GBUniversity of Louisville · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Acute inflammation can either resolve through immunosuppression or persist, leading to chronic inflammation. These transitions are driven by distinct molecular and metabolic reprogramming of immune cells. The anti-diabetic drug Metformin inhibits acute and chronic inflammation through mechanisms still not fully understood. Here, we report that the anti-inflammatory and reactive-oxygen-species-inhibiting effects of Metformin depend on the expression of the plasticity factor ZEB1 in macrophages. Using mice lacking Zeb1 in their myeloid cells and human patient samples, we show that ZEB1 plays a dual role, being essential in both initiating and resolving inflammation by inducing macrophages to transition into an immunosuppressed state. ZEB1 mediates these diverging effects in inflammation and immunosuppression by modulating mitochondrial content through activation of autophagy and inhibition of mitochondrial protein translation. During the transition from inflammation to immunosuppression, Metformin mimics the metabolic reprogramming of myeloid cells induced by ZEB1. Mechanistically, in immunosuppression, ZEB1 inhibits amino acid uptake, leading to downregulation of mTORC1 signalling and a decrease in mitochondrial translation in macrophages. These results identify ZEB1 as a driver of myeloid cell metabolic plasticity, suggesting that targeting its expression and function could serve as a strategy to modulate dysregulated inflammation and immunosuppression.

Indexed as

MacrophagesMetforminAnimalsHumansImmunosuppression TherapyInflammationMiceMyeloid CellsMetformin

Identifiers

PMID37978290
PMCPMC10656499
OpenAlexW4388750790

What Socratic 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 Socratic graph.