ArticleNature metabolism2023
PFKFB2-mediated glycolysis promotes lactate-driven continual efferocytosis by macrophages.
Article in Nature metabolism, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers.
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Who cites it
95 citing papers in PubMed, 126 citations in OpenAlex.
- Genome-wide CRISPR screens identify shared and context-specific regulators of podocyte resistance to oxidative injury.Renal failure · 2026Article
- Efferocytosis activates a DNMT3A-mediated oxidized DNA repair pathway to enable tissue resolution.The Journal of clinical investigation · 2026Article
- Dynamic metabolic programming of monocyte-derived cells defines immunity in CNS disease.Brain : a journal of neurology · 2026Review
- Bioelectric signals promote diabetic bone regeneration through Piezo1-mediated activation of the efferocytic immune microenvironment.Bioactive materials · 2026Article
- Impaired Glycolysis Leads to Defective Efferocytosis and Impaired Plaque Resolution inCirculation · 2026Article
- Review
- Orchestrating glucose metabolism: PFKFB2 as a signal-integrating conductor in homeostasis and disease.The Journal of biological chemistry · 2026Review
- Chronic inflammation-responsive hydrogel restores myeloid-T cell crosstalk to reinvigorate antitumor immunity against metastatic colorectal cancer.Bioactive materials · 2026Article
- Myeloid PKM2 deficiency alleviates allergic airway inflammation and promotes macrophage efferocytosis via SLC13A3.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- 4-Octyl Itaconate Promotes Diabetic Wound Healing by Enhancing Pro-Resolving Macrophages via the Efferocytosis-MCT1-Lactate-GPR132 Pathway and Macrophage-Independent Synergistic Effects.Diabetes & metabolism journal · 2026Article
- Defective efferocytosis in diabetes: molecular mechanisms and emerging therapeutic strategies.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Ferroptosis-driven immune remodeling in heart failure: the central role of macrophage reprogramming and impaired efferocytosis.Journal of nanobiotechnology · 2026Review
- Extracellular Vesicle-Transferred ATP-Citrate Lyase Induces Monocyte Differentiation Toward Tumor-Associated Macrophages and Fuels Hepatocellular Carcinoma Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Ginsenoside Rg1 alleviates post-ischemic stroke neuroinflammation by inhibiting CKLF1-mediated suppression of dead/dying neuron clearance.Acta pharmaceutica Sinica. B · 2026Article
- Macrophage efferocytosis promotes inflammation resolution and accelerates wound healing.Communications biology · 2026Review
- Review
- Rapid Remodeling of the Human Gut Microbiome in Response to Short-Term Animal Product Restriction and Associations with Host Molecular Phenotypes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Obesity Disrupts H3K4me3-Mediated Lactate Accumulation and Efferocytosis in Hypoxic Macrophages.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- The Metabolite Differences in Vascular Smooth Muscle Cells of Abdominal Aortic Aneurysm Revealed by Untargeted Metabolomics.Biomedicines · 2026Article
- Polystyrene microplastic-induced pathophysiology is driven by disruption of efferocytosis.Immunity · 2026Article
35 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Resolving-type macrophages prevent chronic inflammation by clearing apoptotic cells through efferocytosis. These macrophages are thought to rely mainly on oxidative phosphorylation, but emerging evidence suggests a possible link between efferocytosis and glycolysis. To gain further insight into this issue, we investigated molecular-cellular mechanisms involved in efferocytosis-induced macrophage glycolysis and its consequences. We found that efferocytosis promotes a transient increase in macrophage glycolysis that is dependent on rapid activation of the enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2 (PFKFB2), which distinguishes this process from glycolysis in pro-inflammatory macrophages. Mice transplanted with activation-defective PFKFB2 bone marrow and then subjected to dexamethasone-induced thymocyte apoptosis exhibit impaired thymic efferocytosis, increased thymic necrosis, and lower expression of the efferocytosis receptors MerTK and LRP1 on thymic macrophages compared with wild-type control mice. In vitro mechanistic studies revealed that glycolysis stimulated by the uptake of a first apoptotic cell promotes continual efferocytosis through lactate-mediated upregulation of MerTK and LRP1. Thus, efferocytosis-induced macrophage glycolysis represents a unique metabolic process that sustains continual efferocytosis in a lactate-dependent manner. The differentiation of this process from inflammatory macrophage glycolysis raises the possibility that it could be therapeutically enhanced to promote efferocytosis and resolution in chronic inflammatory diseases.
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Registered trials
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.