ArticleImmunity2021
IL-33-induced metabolic reprogramming controls the differentiation of alternatively activated macrophages and the resolution of inflammation.
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Article in Immunity, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 121 papers.
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121citing papers in PubMed
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121 citing papers in PubMed, 190 citations in OpenAlex.
- Dynamic metabolic programming of monocyte-derived cells defines immunity in CNS disease.Brain : a journal of neurology · 2026Review
- Alox15 restrains glycolysis to support M2 macrophage effector function during helminth immunity.The Journal of experimental medicine · 2026Article
- Coenzyme A activates TLR4 and enhances alternative macrophage activation in line with MyD88 agonism.EMBO reports · 2026Article
- Interleukin-33 and its receptor: multifaceted roles and emerging therapeutic potential.Nature reviews. Immunology · 2026Review
- The IL-33/ST2 pathway to modulate the inflammatory microenvironment: A new therapeutic target in chronic obstructive pulmonary disease.Biochemistry and biophysics reports · 2026Review
- Histidine metabolic reprogramming drives oxidative stress induced mtDNA release to promote necroptosis and airway inflammation in severe asthma.Redox biology · 2026Article
- Neutrophil-based immunotherapy: A metabolic lens on mechanisms and therapeutic implications.Clinical and translational medicine · 2026Review
- Macrophage-derived itaconate is a negative regulator of adipose tissue thermogenesis.Nature metabolism · 2026Article
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- Metabolic Perspective on Atherosclerosis: Macrophage Reprogramming and Novel Therapeutic Targets.Journal of the American Heart Association · 2026Review
- Pro- and Anti-Inflammatory Macrophages Adjust UCP2 Protein Levels Based on Their Intrinsic Metabolism and Available Metabolites.European journal of immunology · 2026Article
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- Spatial single-cell landscape of tumor-associated macrophages and their crosstalk with the tumor microenvironment.Cell discovery · 2026Article
- Effects of Simulated Typhoon Stress on Ovarian Function in Wenchang Chickens: An Exploration Based on the Microbiota-Gut-Brain-Ovarian Axis.Animals : an open access journal from MDPI · 2026Article
- Hdac11 promotes idiopathic pulmonary fibrosis through macrophage M2-type polarization and myofibroblast accumulation by inhibiting Parkin-dependent mitophagy.Nature communications · 2026Article
- Pollutant particles enhance house dust mite induced type 2 inflammation and the recruitment of monocyte derived Cd11cParticle and fibre toxicology · 2026Article
- GATA2 controls alveolar macrophage inflammatory gene expression and metabolic function.JCI insight · 2026Article
- CD5L insufficiency exacerbates skeletal joint damage in rheumatoid arthritis.Molecular medicine (Cambridge, Mass.) · 2026Article
- Perivascular mesenchymal cells instruct ST2+ reparative macrophages to promote endovascular injury-induced neointimal hyperplasia in mice.Nature communications · 2026Article
61 more citing papers are in PubMed but not listed here.
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Authors and funding
26 authors at 3 institutions in 3 countries.
Maria FaasDepartment of Internal Medicine 3 - Rheumatology and Immunology, Friedrich-Alexander University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen 91054, Germany; Deutsches Zentrum für Immuntherapie (DZI), Friedrich-Alexander University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen 91054, Germany.
Natacha IpseizDepartment of Internal Medicine 3 - Rheumatology and Immunology, Friedrich-Alexander University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen 91054, Germany; Deutsches Zentrum für Immuntherapie (DZI), Friedrich-Alexander University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen 91054, Germany; Systems Immunity Research Institute, Heath Park, Cardiff University, Cardiff CF14 4XN, UK.
Jochen AckermannDepartment of Internal Medicine 3 - Rheumatology and Immunology, Friedrich-Alexander University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen 91054, Germany; Deutsches Zentrum für Immuntherapie (DZI), Friedrich-Alexander University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen 91054, Germany.
Stephan CulemannDepartment of Internal Medicine 3 - Rheumatology and Immunology, Friedrich-Alexander University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen 91054, Germany; Deutsches Zentrum für Immuntherapie (DZI), Friedrich-Alexander University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen 91054, Germany.
Anika GrüneboomDepartment of Biopsectroscopy, Leibniz-Institut für Analytische Wissenschaften-ISAS-e.V., Dortmund 44139, Germany; Medical Faculty, University Hospital, University Duisburg-Essen, Essen 45147, Germany.
Fenja SchröderDepartment of Internal Medicine 3 - Rheumatology and Immunology, Friedrich-Alexander University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen 91054, Germany; Deutsches Zentrum für Immuntherapie (DZI), Friedrich-Alexander University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen 91054, Germany.
Tobias RotheDepartment of Internal Medicine 3 - Rheumatology and Immunology, Friedrich-Alexander University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen 91054, Germany; Deutsches Zentrum für Immuntherapie (DZI), Friedrich-Alexander University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen 91054, Germany.
Carina ScholtysekDepartment of Internal Medicine 3 - Rheumatology and Immunology, Friedrich-Alexander University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen 91054, Germany; Deutsches Zentrum für Immuntherapie (DZI), Friedrich-Alexander University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen 91054, Germany.
Martin EberhardtDeutsches Zentrum für Immuntherapie (DZI), Friedrich-Alexander University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen 91054, Germany; Laboratory of Systems Tumor Immunology, Department of Dermatology, Universitätsklinikum Erlangen and Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen 91054, Germany.
Martin BöttcherDeutsches Zentrum für Immuntherapie (DZI), Friedrich-Alexander University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen 91054, Germany; Department of Internal Medicine 5, Friedrich-Alexander University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen 91054, Germany.
Philipp KirchnerInstitute of Human Genetics, Friedrich-Alexander University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen 91054, Germany.
Cornelia StollDepartment of Internal Medicine 3 - Rheumatology and Immunology, Friedrich-Alexander University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen 91054, Germany; Deutsches Zentrum für Immuntherapie (DZI), Friedrich-Alexander University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen 91054, Germany.
Arif EkiciInstitute of Human Genetics, Friedrich-Alexander University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen 91054, Germany.
Maximilian FuchsDepartment of Medical Informatics, Friedrich-Alexander University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen 91054, Germany.
Meik KunzDepartment of Medical Informatics, Friedrich-Alexander University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen 91054, Germany.
Benno WeigmannDeutsches Zentrum für Immuntherapie (DZI), Friedrich-Alexander University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen 91054, Germany; Department of Internal Medicine 1, Friedrich-Alexander University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen 91054, Germany.
Stefan WirtzDeutsches Zentrum für Immuntherapie (DZI), Friedrich-Alexander University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen 91054, Germany; Department of Internal Medicine 1, Friedrich-Alexander University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen 91054, Germany.
Roland LangInstitute of Clinical Microbiology, Friedrich-Alexander University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen 91054, Germany.
Joerg HofmannDivision of Biochemistry, Department of Biology, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen 91054, Germany.
Julio VeraDeutsches Zentrum für Immuntherapie (DZI), Friedrich-Alexander University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen 91054, Germany; Laboratory of Systems Tumor Immunology, Department of Dermatology, Universitätsklinikum Erlangen and Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen 91054, Germany.
David VoehringerDivision of Infection Biology, Institute of Clinical Microbiology, Friedrich-Alexander University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen 91054, Germany.
Alessandro MichelucciNeuro-Immunology Group, Department of Oncology, Luxembourg Institute of Health (LIH), Luxembourg 1526, Luxembourg.
Dimitrios MougiakakosDeutsches Zentrum für Immuntherapie (DZI), Friedrich-Alexander University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen 91054, Germany; Department of Internal Medicine 5, Friedrich-Alexander University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen 91054, Germany.
Stefan UderhardtDepartment of Internal Medicine 3 - Rheumatology and Immunology, Friedrich-Alexander University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen 91054, Germany; Deutsches Zentrum für Immuntherapie (DZI), Friedrich-Alexander University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen 91054, Germany.
Georg SchettDepartment of Internal Medicine 3 - Rheumatology and Immunology, Friedrich-Alexander University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen 91054, Germany; Deutsches Zentrum für Immuntherapie (DZI), Friedrich-Alexander University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen 91054, Germany.
Gerhard KrönkeDepartment of Internal Medicine 3 - Rheumatology and Immunology, Friedrich-Alexander University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen 91054, Germany; Deutsches Zentrum für Immuntherapie (DZI), Friedrich-Alexander University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen 91054, Germany. Electronic address: gerhard.kroenke@uk-erlangen.de.
Friedrich-Alexander-Universität Erlangen-Nürnberg · DELeibniz Institute for Analytical Sciences - ISAS · DELuxembourg Institute of Health · LU
Funding
European Research Council 101001866European Research Council 810316
Abstract
Alternatively activated macrophages (AAMs) contribute to the resolution of inflammation and tissue repair. However, molecular pathways that govern their differentiation have remained incompletely understood. Here, we show that uncoupling protein-2-mediated mitochondrial reprogramming and the transcription factor GATA3 specifically controlled the differentiation of pro-resolving AAMs in response to the alarmin IL-33. In macrophages, IL-33 sequentially triggered early expression of pro-inflammatory genes and subsequent differentiation into AAMs. Global analysis of underlying signaling events revealed that IL-33 induced a rapid metabolic rewiring of macrophages that involved uncoupling of the respiratory chain and increased production of the metabolite itaconate, which subsequently triggered a GATA3-mediated AAM polarization. Conditional deletion of GATA3 in mononuclear phagocytes accordingly abrogated IL-33-induced differentiation of AAMs and tissue repair upon muscle injury. Our data thus identify an IL-4-independent and GATA3-dependent pathway in mononuclear phagocytes that results from mitochondrial rewiring and controls macrophage plasticity and the resolution of inflammation.
Indexed as
Energy MetabolismBiomarkersCell DifferentiationInflammationInterleukin-33Macrophage ActivationMacrophagesMitochondriaPhagocytesSignal TransductionBiomarkersInterleukin-33alternatively activated macrophageGATA3interleukin-33itaconatemitochondrial rewiringresolution of inlammationUCP2uncoupling
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