ArticleCell reports2018
Nuclear Receptor Nur77 Limits the Macrophage Inflammatory Response through Transcriptional Reprogramming of Mitochondrial Metabolism.
Article in Cell reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers.
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Who cites it
86 citing papers in PubMed.
- Targeting NR4A1 (Nur77) in Macrophage Polarization: Molecular Mechanisms and Translational Prospects for Cardiac Repair After Myocardial Infarction.International journal of molecular sciences · 2026Review
- Nuclear receptor Nur77 resolves the inflammatory response of macrophages primarily by regulating expression of AP-1 transcription factors and their target genes.Nucleic acids research · 2026Article
- Review
- Reprogramming macrophage metabolism for cardiovascular therapy: From molecular pathways to precision nanomedicine.Materials today. Bio · 2026Review
- Nur77 agonism invigorates Natural Killer cell immunity against hepatocellular carcinoma.Nature communications · 2026Article
- APOE4 Drives Uniquely Dysfunctional Human Microglial States in Alzheimer's Disease.bioRxiv : the preprint server for biology · 2026Article
- Vancomycin disrupts mitochondrial morphology and function and impairs macrophage fungal killing.mBio · 2026Article
- OGDH primes macrophage for M1-like polarization and ferroptosis in sepsis associated acute lung injury.Respiratory research · 2026Article
- Mechanistic Investigation of Vitexin in Ameliorating Ovarian Fibrosis in PCOS Mice via the NR4A1/NLRP3 Signaling Pathway.Metabolites · 2026Article
- The Circadian Rhythm Regulates the Hepato-ovarian Axis Linking Polycystic Ovary Syndrome and Non-alcoholic Fatty Liver Disease.Biochemical genetics · 2026Article
- Oxytocin Modulates Microglial IL-17-Linked Inflammatory Pathways Through the IL-6/COX-2.Life (Basel, Switzerland) · 2026Article
- Peripheral blood microarray-based transcriptomic and epigenetic analyses identify immune, inflammation, and metabolic dysregulation in Alzheimer's disease.NPJ dementia · 2026Article
- Tumor-immune metabolic tug-of-war: from immune escape to targeting metabolic rewiring in cancer therapy.Frontiers in cell and developmental biology · 2026Review
- From injury to recovery: transcriptomic dynamics in zebrafish brain regeneration.Journal of translational medicine · 2025Article
- Nuclear receptors in health and disease: signaling pathways, biological functions and pharmaceutical interventions.Signal transduction and targeted therapy · 2025Review
- Essential role of the metabolite α-ketoglutarate in bone tissue and bone-related diseases.Acta biochimica et biophysica Sinica · 2025Review
- Nr4a1 and Nr4a3 redundantly control clonal deletion and contribute to an anergy-like transcriptome in auto-reactive thymocytes to impose tolerance in mice.Nature communications · 2025Article
- Sustainable Immunomodulatory via Macrophage P2Y12 Inhibition Mediated Bioactive Patche for Peritendinous Antiadhesion.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Potential Role of NUR77 in the Aging Retinal Pigment Epithelium and Age-Related Macular Degeneration.Advances in experimental medicine and biology · 2025Review
- Nuclear receptor 4A1 is critical for neutrophil-dependent pulmonary immunity toFrontiers in immunology · 2025Article
26 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
15 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activation of macrophages by inflammatory stimuli induces reprogramming of mitochondrial metabolism to support the production of pro-inflammatory cytokines and nitric oxide. Hallmarks of this metabolic rewiring are downregulation of α-ketoglutarate formation by isocitrate dehydrogenase (IDH) and accumulation of glutamine-derived succinate, which enhances the inflammatory response via the activity of succinate dehydrogenase (SDH). Here, we identify the nuclear receptor Nur77 (Nr4a1) as a key upstream transcriptional regulator of this pro-inflammatory metabolic switch in macrophages. Nur77-deficient macrophages fail to downregulate IDH expression and accumulate higher levels of succinate and other TCA cycle-derived metabolites in response to inflammatory stimulation in a glutamine-independent manner. Consequently, these macrophages produce more nitric oxide and pro-inflammatory cytokines in an SDH-dependent manner. In vivo, bone marrow Nur77 deficiency exacerbates atherosclerosis development and leads to increased circulating succinate levels. In summary, Nur77 induces an anti-inflammatory metabolic state in macrophages that protects against chronic inflammatory diseases such as atherosclerosis.
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