ArticleThe Journal of clinical investigation2023
The immunometabolite itaconate stimulates OXGR1 to promote mucociliary clearance during the pulmonary innate immune response.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 61 citations in OpenAlex.
- 4-Octyl Itaconate Attenuates Age-Induced Parotid Gland Dysfunction Through the Suppression of Fibrosis and Lipid Deposition by AMPKα/PPARα and the Inhibition of Oxidative Stress via the AMPKα/Nrf2 Signaling Pathway.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Itaconate and its derivatives in human health and diseases.Signal transduction and targeted therapy · 2026Review
- Metabolic Bottlenecks and Opportunities: Reshaping the Tumor Microenvironment for Cancer Immunotherapy.Cells · 2026Review
- Macrophage-derived itaconate is a negative regulator of adipose tissue thermogenesis.Nature metabolism · 2026Article
- Metabolite and nutrient regulation of macrophages in obesity and metabolic disease.Nature reviews. Immunology · 2026Review
- Structural insights into ligand recognition and activation of the human oxoglutarate receptor OXGR1.Nature communications · 2026Article
- Molecular architecture of OXGR1 reveals an evolutionary conserved mechanisms for metabolite surveillance.The EMBO journal · 2026Article
- Obesity suppresses neutrophil-dependent itaconate signaling promoting ferroptosis in acute pancreatitis.Redox biology · 2026Article
- Offense and defense: itaconate mediates bidirectional immune regulation of host-bacteria interaction.Journal of biomedical science · 2026Review
- iNOS modulates inflammatory responses in an NO-independent manner through direct interaction with IRG1 in mitochondria.Nature metabolism · 2026Article
- Mitochondrial iNOS blocks itaconate production by interacting with IRG1.Nature metabolism · 2026Article
- Design, Synthesis, and Characterization ofACS omega · 2026Article
- Tuft cells shape airway remodeling by eliciting OXGR1- and SOX9-dependent stem cell programs.Nature communications · 2026Article
- Structural analysis reveals that water molecules mediate self-activation of GPR99.Communications biology · 2026Article
- Itaconate and its derivatives ameliorate autoimmunity by suppressing Th17 cells via regulating mitophagy.Cell communication and signaling : CCS · 2026Article
- Mediterranean Pattern Diet in Multiple Sclerosis: A Review Focusing on Immunometabolites.Current neuropharmacology · 2026Review
- Alpha-ketoglutarate Potentiates IL-1β Production and Suppressive Mechanisms of Myeloid-Derived Suppressor Cells by Altering Redox Metabolism and Inducing Autophagy.International journal of biological sciences · 2026Article
- Adaptive metabolic strategies of intracellular bacterial pathogens.Frontiers in microbiology · 2026Review
- Itaconate Modulates Neutrophil Homeostasis to Ameliorate Airway Inflammation in Diesel Exhaust Particles-exacerbated Asthma via Inhibiting NETs Formation.International journal of biological sciences · 2026Article
- Itaconate transport across the plasma membrane and Salmonella-containing vacuole via MCT1/4 modulates macrophage antibacterial activity.Nature communications · 2025Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pathogens and inflammatory conditions rapidly induce the expression of immune-responsive gene 1 (IRG1) in cells of myeloid lineage. IRG1 encodes an aconitate decarboxylase (ACOD1) that produces the immunomodulatory metabolite itaconate (ITA). In addition to rapid intracellular accumulation, ITA is also secreted from the cell, but whether secreted ITA functions as a signaling molecule is unclear. Here, we identified ITA as an orthosteric agonist of the GPCR OXGR1, with an EC50 of approximately 0.3 mM, which was in the same range as the physiological concentration of extracellular ITA upon macrophage activation. ITA activated OXGR1 to induce Ca2+ mobilization, ERK phosphorylation, and endocytosis of the receptor. In a mouse model of pulmonary infection with bacterial Pseudomonas aeruginosa, ITA stimulated Oxgr1-dependent mucus secretion and transport in respiratory epithelium, the primary innate defense mechanism of the airway. Our study thus identifies ITA as a bona fide ligand for OXGR1 and the ITA/OXGR1 paracrine signaling pathway during the pulmonary innate immune response.
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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.