ArticleJournal of immunology (Baltimore, Md. : 1950)2018
GPR81, a Cell-Surface Receptor for Lactate, Regulates Intestinal Homeostasis and Protects Mice from Experimental Colitis.
Article in Journal of immunology (Baltimore, Md. : 1950), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 116 papers.
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Who cites it
116 citing papers in PubMed, 172 citations in OpenAlex.
- Immunomodulatory Function of Soluble Dietary Fiber: Toward Application for Prevention and Treatment of Food Allergies.Current allergy and asthma reports · 2026Review
- Hypertonic sodium lactate improves microcirculation, modulates inflammation, and preserves vascular reactivity in a rat model of sepsis: in vivo and ex vivo evidence.Intensive care medicine experimental · 2026Article
- Trifluoroacetate mediated reduction of atherosclerosis in mice.Nature communications · 2026Article
- Exercise-Mediated Molecular Mechanisms of Antidepressant Effects: The Role of the Microbiota-Gut-Brain Axis.International journal of molecular sciences · 2026Review
- Glycolysis drives vascular hyperpermeability in acute lung injury via lactate-GPR81 axis in endothelial cells.Cell communication and signaling : CCS · 2026Article
- Metabolic reprogramming of myeloid cells in cancer: from lactate-NAMPT axis to AI-guided therapeutics.Experimental & molecular medicine · 2026Review
- Functional Integration of Crosstalk Between Probiotic Lactic Acid Bacteria and Intestinal Immunity Signaling.Probiotics and antimicrobial proteins · 2026Review
- Cytokine signalling in vaginal epithelial cells: mechanistic insights into epithelial immunity and inflammatory milieu in vulvovaginal candidiasis.European cytokine network · 2026Review
- Unveiling lactylation: A novel frontier in the pathogenesis of diabetic nephropathy (Review).International journal of molecular medicine · 2026Review
- Metabolites as signalling molecules in the tumour immune microenvironment.Nature reviews. Immunology · 2026Review
- Lactate and lactylation: mechanisms, function, diseases, and therapeutic targets.Molecular biomedicine · 2026Review
- Lactate reprograms PGE2 metabolism via GPR81 inhibits COX2 to relieved psoriasis.Scientific reports · 2026Article
- Postbiotics: Novel Modulators of Gut Health, Metabolism, and Their Mechanisms of Action.Probiotics and antimicrobial proteins · 2026Review
- Lactate: elucidating its indispensable role in human health.Molecular cancer · 2026Review
- Microbiota-derived metabolites in hematopoietic regulation and disease: mechanisms, context, and therapeutic perspectives.Frontiers in microbiology · 2026Review
- Type 2 Inflammatory Diseases: The Crossroads of Immunity and Metabolism.Research (Washington, D.C.) · 2026Review
- Tumor-immune metabolic tug-of-war: from immune escape to targeting metabolic rewiring in cancer therapy.Frontiers in cell and developmental biology · 2026Review
- Casein hydrolysate promotes intestinal repair in adult mice withFrontiers in immunology · 2026Article
- Lactylation in cancer biology: Unlocking new avenues for research and therapy.Cancer communications (London, England) · 2025Review
- Lactate and lactylation in tumor immunity.Frontiers of medicine · 2025Review
56 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
At mucosal sites such as the intestine, the immune system launches robust immunity against invading pathogens while maintaining a state of tolerance to commensal flora and ingested food Ags. The molecular mechanisms underlying this phenomenon remain poorly understood. In this study, we report that signaling by GPR81, a receptor for lactate, in colonic dendritic cells and macrophages plays an important role in suppressing colonic inflammation and restoring colonic homeostasis. Genetic deletion of GPR81 in mice led to increased Th1/Th17 cell differentiation and reduced regulatory T cell differentiation, resulting in enhanced susceptibility to colonic inflammation. This was due to increased production of proinflammatory cytokines (IL-6, IL-1β, and TNF-α) and decreased expression of immune regulatory factors (IL-10, retinoic acid, and IDO) by intestinal APCs lacking GPR81. Consistent with these findings, pharmacological activation of GPR81 decreased inflammatory cytokine expression and ameliorated colonic inflammation. Taken together, these findings identify a new and important role for the GPR81 signaling pathway in regulating immune tolerance and colonic inflammation. Thus, manipulation of the GPR81 pathway could provide novel opportunities for enhancing regulatory responses and treating colonic inflammation.
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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.