ArticleProceedings of the National Academy of Sciences of the United States of America2017
Intracellular metabolite β-glucosylceramide is an endogenous Mincle ligand possessing immunostimulatory activity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers.
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96 citing papers in PubMed, 171 citations in OpenAlex.
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- C-Type lectin receptors as key modulators of intestinal inflammation: insights into IBD pathogenesis and therapy.FEMS microbiology letters · 2026Review
- Mincle-dependent Th17 adjuvanticity requires TNFR1 signaling in myeloid cells.Frontiers in immunology · 2026Article
- Rice-derived glucosylceramides activate innate immune responses in myeloid lineage differentiated dendritic cells via toll-like receptors 2 and 4.Journal of natural medicines · 2026Article
- The β-hCG-TNF-α-T cell axis in threatened abortion: unraveling the pathogenic cascade from aberrant glycosylation to inflammatory demise.Frontiers in immunology · 2026Review
- Altered glycolipid metabolism during acute kidney injury exacerbates renal inflammation.Scientific reports · 2025Article
- Elevated hexosylceramides in Parkinson's disease cause gene upregulations in neurons mimicking responses to pathogens.NPJ Parkinson's disease · 2025Article
- Regulation of IL-10 production in dendritic cells is controlled by the co-activation of TLR2 and Mincle byMicrobiology spectrum · 2025Article
- Raver1 linksProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Substrates, regulation, cellular functions, and disease associations of P4-ATPases.Communications biology · 2025Review
- Multi-omics analysis of the potential association between metabolic features of hypothyroidism in the first half of pregnancy and Th17/Treg balance.Frontiers in immunology · 2025Article
- Small molecules as ligands in the tuning of immune regulatory receptors.Frontiers in immunology · 2025Review
- The Dectin-1 and Dectin-2 clusters: C-type lectin receptors with fundamental roles in immunity.EMBO reports · 2024Review
36 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sensing and reacting to tissue damage is a fundamental function of immune systems. Macrophage inducible C-type lectin (Mincle) is an activating C-type lectin receptor that senses damaged cells. Notably, Mincle also recognizes glycolipid ligands on pathogens. To elucidate endogenous glycolipids ligands derived from damaged cells, we fractionated supernatants from damaged cells and identified a lipophilic component that activates reporter cells expressing Mincle. Mass spectrometry and NMR spectroscopy identified the component structure as β-glucosylceramide (GlcCer), which is a ubiquitous intracellular metabolite. Synthetic β-GlcCer activated myeloid cells and induced production of inflammatory cytokines; this production was abrogated in Mincle-deficient cells. Sterile inflammation induced by excessive cell death in the thymus was exacerbated by hematopoietic-specific deletion of degrading enzyme of β-GlcCer (β-glucosylceramidase, GBA1). However, this enhanced inflammation was ameliorated in a Mincle-deficient background. GBA1-deficient dendritic cells (DCs) in which β-GlcCer accumulates triggered antigen-specific T-cell responses more efficiently than WT DCs, whereas these responses were compromised in DCs from GBA1 × Mincle double-deficient mice. These results suggest that β-GlcCer is an endogenous ligand for Mincle and possesses immunostimulatory activity.
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