Affinage

CLEC4E

C-type lectin domain family 4 member E · UniProt Q9ULY5

Length
219 aa
Mass
25.1 kDa
Annotated
2026-06-09
100 papers in source corpus 43 papers cited in narrative 44 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CLEC4E (Mincle) is a myeloid C-type lectin receptor that couples innate sensing of microbial glycolipids and damage-associated molecules to pro-inflammatory signaling, immune adjuvanticity, and sterile inflammation (PMID:20008526, PMID:20164423). It is a non-signaling receptor that recruits the ITAM-bearing FcRγ chain to assemble a Syk-CARD9-Bcl10-MALT1 signaling complex driving NF-κB-dependent cytokine, chemokine, and nitric oxide production (PMID:18776906, PMID:23921530). Surface display and ligand competence depend on heterodimerization with MCL/Clec4d through a hydrophobic stalk-region interaction, and Mincle is itself transcriptionally induced downstream of TLR4/MyD88 via C/EBPβ and NF-κB/PU.1 binding to its promoter, providing feed-forward amplification (PMID:25202022, PMID:25156364, PMID:25888641, PMID:28017324, PMID:37117184). Crystallographic and structure-activity studies define a Ca2+-dependent sugar-binding site adjacent to a hydrophobic groove that docks the acyl chains of glycolipids, explaining recognition of a broad ligand repertoire including mycobacterial trehalose dimycolate (TDM/cord factor) and the synthetic adjuvant TDB, fungal alpha-mannose structures of Malassezia, streptococcal glucosyl-diacylglycerol and monoglucosyldiacylglycerol, and the human-specific ligand cholesterol crystals (PMID:20008526, PMID:19171887, PMID:24101491, PMID:23960080, PMID:27923071, PMID:28223515, PMID:30352847, PMID:26296894). Mincle also senses endogenous danger signals released from damaged cells—the nuclear protein SAP130, β-glucosylceramide (potentiated by free cholesterol), cholesterol sulfate, and peroxiredoxin-1—linking necroptotic and barrier injury to inflammation across atherosclerosis, acute kidney injury, myocardial reperfusion injury, hepatic injury, psoriasis, uveoretinitis, and tumor-associated macrophage programming (PMID:18776906, PMID:27049944, PMID:28373578, PMID:28292894, PMID:32797195, PMID:37164261, PMID:27587433, PMID:32532809). Downstream of receptor engagement Mincle controls iNOS through both transcription and eIF5A-hypusination-dependent translation, induces ER stress, autophagy and NET formation, and shapes adaptive immunity by promoting Th17 responses, including a T-cell-intrinsic β-glucosylceramide-Mincle-NLRP3 autocrine loop in CNS inflammation (PMID:27089465, PMID:27587433, PMID:28186242, PMID:23308247, PMID:35504893). Certain pathogens co-opt Mincle into an inhibitory ITAMi configuration that recruits SHP1 via FcRγ to dampen dendritic cell activation, and Mincle expression is further restrained post-transcriptionally by miR-219c-3p targeting its 3'-UTR and by CD11b-mediated Syk dephosphorylation (PMID:27742545, PMID:34556635, PMID:29400702).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2008 High

    Established Mincle's core signaling logic and first endogenous danger ligand, answering how a lectin receptor transduces sensing of dead cells into inflammation.

    Evidence Co-IP, reporter assays and Mincle-deficient macrophages identifying FcRγ coupling and SAP130 as a released ligand

    PMID:18776906

    Open questions at the time
    • Did not define the downstream kinase cascade beyond ITAM coupling
    • SAP130 binding mode to the CRD not structurally resolved
  2. 2008 Medium

    Showed the Mincle CRD can bind fungal cells directly, opening the question of which glycan ligands it recognizes.

    Evidence Recombinant refolded CRD binding to Candida albicans cells and yeast extract in vitro

    PMID:18509109

    Open questions at the time
    • No functional signaling follow-up
    • Specific glycan ligand not identified in this study
  3. 2009 High

    Identified Mincle as the essential receptor for mycobacterial cord factor TDM and for fungal alpha-mannose ligands, establishing it as a pattern-recognition receptor for pathogen glycolipids.

    Evidence Lipid fractionation, mannose-binding-motif mutagenesis, glycan arrays, KO macrophages and in vivo granuloma/cytokine assays

    PMID:19171887 PMID:20008526

    Open questions at the time
    • Structural basis of glycolipid binding not yet defined
    • Did not establish the full Syk-CARD9 signaling hierarchy
  4. 2010 High

    Connected TDM/TDB recognition to the Syk-Card9 axis and to vaccine adjuvanticity, defining Mincle as a target for adjuvant design.

    Evidence Mincle-Fc fusion binding assays, KO macrophages and in vivo Th17 vaccination

    PMID:20164423

    Open questions at the time
    • Did not resolve receptor stoichiometry or co-receptor requirements
  5. 2013 High

    Resolved the molecular mechanism of glycolipid recognition, explaining how one receptor accommodates both sugar headgroups and fatty acyl chains.

    Evidence X-ray crystallography of mouse/bovine CRDs with functional and affinity mutagenesis defining Ca2+ site plus a hydrophobic groove

    PMID:23960080 PMID:24101491

    Open questions at the time
    • Human Mincle structure not captured in fully active conformation
    • Full-length receptor and dimer architecture not solved
  6. 2013 High

    Defined the proximal signaling complex and the MCL/FcεRI-γ partnership that controls Mincle expression and phagocytosis.

    Evidence Flow cytometry, reciprocal Co-IP and phagocytosis assays in rat cells; genetic dissection of Syk-CARD9-Bcl10-MALT1 and MyD88/IL-1R adjuvant requirement

    PMID:23308247 PMID:23921530

    Open questions at the time
    • MCL-Mincle stoichiometry not quantified
    • Order of FcRγ versus MCL assembly unresolved at this stage
  7. 2014 High

    Established the transcriptional circuitry for Mincle induction and revealed pathogen subversion of its signaling, distinguishing activating from immunosuppressive outcomes.

    Evidence ChIP of NF-κB/C/EBPβ on the Mincle promoter, Dectin-3/CARD9/Cebpb/Hif1a KO macrophages with retroviral rescue, and Fonsecaea-driven Mdm2-mediated IRF1 degradation in human DCs

    PMID:24721577 PMID:25156364 PMID:25202022

    Open questions at the time
    • Interplay between NFAT and NF-κB arms not fully delineated
    • HIF1α-independent Mincle induction mechanism partially defined
  8. 2015 High

    Defined how MCL controls Mincle trafficking and extended the ligand repertoire to a human-specific sterol ligand.

    Evidence Stalk-region MCL4S mutagenesis with KO/transgenic rescue; MS identification of cholesterol crystals as a human Mincle ligand; two-step surface translocation model

    PMID:25888641 PMID:26296894 PMID:27005451

    Open questions at the time
    • Mouse-human species divergence in sterol recognition mechanistically unexplained
    • Trafficking machinery for the heterodimer not identified
  9. 2016 High

    Generalized Mincle as a driver of sterile and tumoral inflammation across organs and revealed both inhibitory ITAMi signaling and a translational control branch.

    Evidence KO/chimera models in atherosclerosis, pancreatic cancer, alcoholic liver injury, subarachnoid hemorrhage and uveoretinitis; SHP1 conditional KO and Co-IP for ITAMi; eIF5A-hypusination analysis for iNOS translation

    PMID:26921309 PMID:27049944 PMID:27089465 PMID:27587433 PMID:27628766 PMID:27742545 PMID:27845194 PMID:28017324

    Open questions at the time
    • What dictates the switch between activating and ITAMi configurations is not resolved
    • Direct binding of all endogenous ligands (e.g. albumin) to the CRD not structurally validated
  10. 2017 High

    Identified β-glucosylceramide and cholesterol sulfate as endogenous Mincle ligands and expanded effector outputs to autophagy/NET formation and Fc-receptor crosstalk.

    Evidence MS/NMR ligand identification with GBA1×Mincle double-KO mice; cholesterol sulfate KO dermatitis model; autophagy-dependent NET assays; CD11b-Mincle and TDM-bead phagosome inhibition; SAR with synthetic glycolipids

    PMID:27923071 PMID:28186242 PMID:28223515 PMID:28292894 PMID:28373578 PMID:28384255 PMID:29400702

    Open questions at the time
    • How free cholesterol potentiates β-GlcCer recognition was not yet defined
    • Negative regulation by CD11b-SHP1 not validated in vivo
  11. 2019 High

    Defined Mincle's homeostatic role in sensing commensals and an autophagy-driven antimicrobial program, broadening it beyond acute pathogen sensing.

    Evidence Mincle-/- and CD11c-Syk conditional KO intestinal models; CLEC4E+TLR4 co-stimulation driving autophagy and Mtb killing in autophagy-deficient macrophages

    PMID:30709742 PMID:31462144

    Open questions at the time
    • Specific commensal glycolipid ligand(s) in the gut not identified
    • Mechanism linking Mincle to lysosome biogenesis incompletely mapped
  12. 2020 High

    Established Mincle as a tunable driver of TAM polarization and tissue injury and demonstrated a synergistic endogenous ligand combination.

    Evidence scRNA-seq and ultrasound-microbubble Mincle silencing in tumor models; β-GlcCer plus free cholesterol synergy in KO kidney ischemia-reperfusion; Syk-NF-κB colitis pyroptosis model

    PMID:32333776 PMID:32532809 PMID:32797195

    Open questions at the time
    • Molecular basis of cholesterol-β-GlcCer synergy at the CRD not structurally resolved
    • TAM-intrinsic Mincle ligand in tumors not defined
  13. 2021 High

    Defined post-transcriptional control of Mincle and extended its injury role to the heart.

    Evidence Luciferase 3'-UTR reporter and lentiviral miR-219c-3p overexpression in AKI; Clec4e-/- myocardial ischemia-reperfusion with human/porcine expression correlation

    PMID:34466750 PMID:34556635

    Open questions at the time
    • Upstream regulators of miR-219c-3p not identified
    • Cell-type source of cardiac Mincle ligand not defined
  14. 2023 High

    Identified peroxiredoxin-1 as a new DAMP ligand and consolidated the Mincle-Syk-NF-κB axis as a macrophage-driven disease mechanism with therapeutic tractability.

    Evidence Co-IP of Prdx1-Mincle with KO/recombinant rescue in AKI; macrophage-specific Mincle KO, PU.1-dependent induction and neutralizing antibody in psoriasis

    PMID:37117184 PMID:37164261

    Open questions at the time
    • Prdx1 binding site on the CRD not structurally mapped
    • Generality of antibody-based Mincle blockade across diseases untested here
  15. 2025 Medium

    Extended Mincle function to instruction of trained immunity in bone marrow progenitors following barrier disruption.

    Evidence Clec4e-/- mice with DSS permeability and heat-killed E. faecalis trained-immunity readouts

    PMID:39848243

    Open questions at the time
    • Single lab
    • Bacterial ligand engaging Mincle in this context not chemically defined
    • Epigenetic mediators of the trained phenotype not mapped

Open questions

Synthesis pass · forward-looking unresolved questions
  • What governs the molecular switch between Mincle's activating ITAM and inhibitory ITAMi configurations, and how distinct endogenous and microbial ligands bias this choice, remains unresolved.
  • No structural model of full-length Mincle-MCL-FcRγ signaling complex
  • Determinants of SHP1 versus Syk recruitment by FcRγ not defined
  • Mechanism distinguishing pro-inflammatory from immunosuppressive outcomes per ligand unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008289 lipid binding 7 GO:0038024 cargo receptor activity 4 GO:0060089 molecular transducer activity 3 GO:0140096 catalytic activity, acting on a protein 2
Localization
GO:0005886 plasma membrane 4
Pathway
R-HSA-168256 Immune System 7 R-HSA-162582 Signal Transduction 6 R-HSA-1643685 Disease 5 R-HSA-8953897 Cellular responses to stimuli 2 R-HSA-9612973 Autophagy 2
Partners
CARD9CLEC4DFCER1GITGAMPRDX1PTPN6SAP130SYK
Complex memberships
Mincle-CD11b inhibitory complexMincle-FcRγ ITAM signaling complexMincle-MCL (Clec4d) heterodimer

Evidence

Reading pass · 44 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2008 Mincle selectively associates with the Fc receptor common gamma-chain (FcRγ) to form an ITAM-coupled signaling complex, enabling macrophage activation to produce inflammatory cytokines and chemokines upon sensing dead cells. Co-immunoprecipitation, reporter cell assays, Mincle-deficient macrophages Nature immunology High 18776906
2008 SAP130, a component of small nuclear ribonucleoprotein released from dead cells, is identified as an endogenous Mincle ligand that triggers inflammatory responses. Biochemical fractionation of dead cell supernatants, reporter cell activation assays, in vivo neutrophil infiltration assay with Mincle-blocking antibody Nature immunology High 18776906
2008 Human and mouse Mincle carbohydrate-recognition domains (CRDs) bind to Candida albicans yeast cells and yeast extract in vitro. Recombinant CRD expression, refolding, binding assays with whole yeast cells and yeast extract Glycobiology Medium 18509109
2009 Mincle is an essential receptor for the mycobacterial glycolipid trehalose-6,6'-dimycolate (TDM/cord factor); Mincle-deficient macrophages completely fail to produce inflammatory cytokines and nitric oxide in response to TDM, and Mincle-deficient mice do not form TDM-induced lung granulomas. Lipid fractionation of heat-killed mycobacteria, Mincle-deficient macrophage assays, in vivo TDM administration in Mincle-knockout mice The Journal of experimental medicine High 20008526
2009 Mincle specifically recognizes Malassezia species among 50 fungal species tested; recognition requires the putative mannose-binding motif in the C-type lectin domain; Mincle selectively binds alpha-mannose but not mannan; Mincle-deficient macrophages show significantly impaired cytokine/chemokine production in response to Malassezia. NFAT-GFP reporter cell screening of 50 fungal species, site-directed mutagenesis of mannose-binding motif, glycoconjugate microarray, Mincle-deficient mouse macrophages Proceedings of the National Academy of Sciences of the United States of America High 19171887
2010 Mincle, together with FcRγ adaptor, is the receptor for TDM and TDB that drives Syk-Card9 signaling in APCs; genetic ablation of Mincle abolishes TDM/TDB-induced macrophage activation and Th17 adjuvanticity in vivo. Recombinant Mincle-Fc fusion protein binding assays, Mincle-knockout macrophages, in vivo vaccination with tuberculosis subunit vaccine Journal of immunology High 20164423
2013 Crystal structure of Mincle reveals a Ca2+-dependent sugar-binding site and a unique adjacent shallow hydrophobic groove that accommodates fatty acid moieties of glycolipids; mutagenesis of the hydrophobic region abolishes glycolipid recognition. X-ray crystallography of Mincle CRD and Mincle-citric acid complex, functional mutagenesis with glycolipid ligands Proceedings of the National Academy of Sciences of the United States of America High 24101491
2013 Crystallographic and mutagenesis analysis of bovine mincle CRD defines an extended binding site: one glucose of trehalose is Ca2+-liganded (as in other C-type lectins), a secondary binding site contacts the second glucose (36-fold higher affinity for trehalose vs. glucose), and an adjacent hydrophobic groove docks one acyl chain of TDM. X-ray crystallography, site-directed mutagenesis, binding studies with glycolipid mimics, affinity measurements The Journal of biological chemistry High 23960080
2013 Mincle signals via the Syk-CARD9-Bcl10-MALT1 pathway by recruiting the ITAM-bearing FcεRI-γ; Mincle and MCL form heteromers on the cell surface, and association with MCL and FcεRI-γ increases Mincle expression and enhances phagocytosis. Flow cytometry, co-immunoprecipitation, cell surface biochemical analysis in rat primary cells and cell lines European journal of immunology Medium 23921530
2013 TDB adjuvant triggers Mincle-dependent IL-1 production that then activates MyD88/IL-1R signaling to drive Th1/Th17 adaptive responses in vivo; the adjuvant effect requires both the Mincle-FcRγ-Syk-Card9 axis and MyD88-dependent IL-1R signaling. Mincle-knockout mice, MyD88-deficient mice, IL-1R-deficient mice, ASC-deficient mice, in vivo vaccination PloS one High 23308247
2014 Fonsecaea monophora engages Mincle to activate a Syk-CARD9-PKB signaling cascade that recruits the E3 ubiquitin ligase Mdm2, leading to proteasomal degradation of nuclear IRF1 and thereby blocking IL12A transcription and TH1 responses. Mincle-blocking experiments in human DCs, Syk inhibition, PKB pathway dissection, IRF1 nuclear localization assays, gene expression analysis Cell host & microbe High 24721577
2014 Dectin-3 (MCL/Clec4d)-induced Mincle expression requires CARD9-BCL10-MALT1-dependent NF-κB activation; NF-κB (but not NFAT) binds the Mincle promoter to drive transcription in response to TDM stimulation. Dectin-3-deficient bone marrow macrophages, NF-κB and NFAT inhibitors, chromatin immunoprecipitation (NF-κB binding to Mincle promoter), CARD9-deficient mice The Journal of biological chemistry High 25202022
2014 Human mincle CRD ligand-binding mechanism closely resembles bovine mincle: one glucose of trehalose is Ca2+-liganded, the second glucose contacts a secondary site, and acyl chains enhance affinity; mutagenesis and synthetic analogs confirm the available human mincle crystal structure is not in a fully active conformation. Site-directed mutagenesis of human mincle, binding studies with synthetic TDM analogs, structural comparison with bovine mincle crystal structure Glycobiology Medium 25028392
2014 C/EBPβ is required for Mincle expression and TDB/TDM-induced inflammatory gene transcription in macrophages; HIF1α is downstream of C/EBPβ and controls Nos2 (nitric oxide) expression but is not required for Mincle expression or kinase activation; LPS-priming induces Mincle via MYD88-dependent C/EBPβ upregulation. Microarray, Cebpb-deficient macrophages, retroviral rescue of Mincle in Cebpb-KO cells, Hif1a-deficient macrophages, kinase activation assays Journal of immunology High 25156364
2015 MCL (Clec4d) promotes Mincle surface expression through direct protein-protein interaction via the stalk region; the hydrophobic repeat in MCL's stalk region is necessary and sufficient, and substituting four hydrophobic residues with serine (MCL4S) abolishes the ability to enhance Mincle surface expression and restore TDM responses. MCL-deficient and MCL-transgenic BMDCs, co-immunoprecipitation, stalk-region mutant MCL4S, retroviral rescue, flow cytometry for surface Mincle Journal of immunology High 25888641
2015 Human Mincle (but not murine Mincle) binds cholesterol crystals and triggers innate immune inflammatory responses; murine macrophages transfected with human Mincle respond to cholesterol crystals with pro-inflammatory cytokine production, blocked by anti-human Mincle antibody. Lipid fractionation of liver extracts, MS structural identification, reporter cell assays with hMincle, anti-Mincle antibody blockade, transfection of hMincle into murine macrophages The Journal of biological chemistry Medium 26296894
2015 Microbial stimulation drives Mincle surface expression through the MyD88 signaling pathway; MCL is constitutively expressed but retained intracellularly until Mincle is induced, whereupon the two receptors form heterodimers that translocate to the cell surface ('two-step' model). MyD88-deficient macrophages, MCL-deficient cells, surface expression analysis by flow cytometry and subcellular fractionation Microbes and infection Medium 27005451
2016 Leishmania triggers a Mincle-dependent inhibitory ITAMi (inhibitory ITAM) signaling configuration characterized by SHP1 coupling to the FcRγ chain in DCs, impairing DC activation, migration, and priming of adaptive immunity; selective loss of SHP1 in CD11c+ cells phenocopies enhanced immunity. Mincle-deficient mice, SHP1 conditional KO in CD11c+ cells, co-immunoprecipitation of SHP1 with FcRγ, in vivo Leishmania major infection model Immunity High 27742545
2016 Clec4e (Mincle) signaling in macrophages inhibits cholesterol efflux and induces Syk-mediated endoplasmic reticulum stress (requiring Chop and Ire1a), leading to proinflammatory mediator and growth factor production; Clec4e-/- bone marrow transplant into Ldlr-/- mice reduces lipid accumulation, ER stress, inflammation, and atherosclerosis. Clec4e-deficient macrophages, bone marrow transplantation into Ldlr-/- mice, Chop- and Ire1a-deficient macrophages, cholesterol efflux assays, Syk inhibition Circulation High 27587433
2016 Mincle signaling on M1 macrophages is regulated by TLR4/NF-κB: NF-κB/p65 binds the Mincle promoter in LPS-primed macrophages, blocking TLR4 or NF-κB suppresses LPS-induced Mincle expression; Mincle maintains M1 inflammatory phenotype (IL-1β, MCP-1, iNOS) through Syk signaling. ChIP (NF-κB/p65 binding to Mincle promoter), TLR4 and NF-κB inhibitors, Mincle knockdown, Syk inhibition, adoptive transfer of Mincle+ M1 macrophages Kidney international High 28017324
2016 RIP1/RIP3 necrosome signaling drives cytoplasmic SAP130 expression in pancreatic cancer cells; Mincle on tumor-infiltrating myeloid cells ligated by SAP130 promotes immune-suppressive macrophage function and oncogenesis; Mincle deletion reprograms the tumor microenvironment to enable T cell-mediated anti-tumor immunity. RIP3-knockout and RIP1-inhibited mouse PDA models, Mincle-knockout mice, SAP130 blockade, bone marrow/cellular depletion experiments Nature High 27049944
2016 Mincle activation by SAP130 (from necroptotic cells) drives microglial innate immune responses after subarachnoid hemorrhage; albumin directly binds Mincle and inhibits Mincle/Syk/IL-1β signaling, reducing neuroinflammation. Co-immunoprecipitation (albumin-Mincle interaction), Mincle knockdown in BV-2 microglia, SAP130 stimulation assays, in vivo SAH rat model Brain, behavior, and immunity Medium 27845194
2016 IRAKM Myddosome formed in response to low-dose LPS upregulates Mincle expression in macrophages; Mincle-deficient mice are protected from ethanol-induced liver injury; SAP130 released by ethanol-damaged hepatocytes synergizes with LPS to activate Mincle-dependent inflammasome in macrophages. IRAKM-deficient and Mincle-deficient mice, ethanol liver injury model, ex vivo bone marrow macrophage stimulation, hepatocyte-macrophage co-culture Hepatology High 27628766
2016 Mincle-mediated signaling promotes granuloma resolution by enhancing translation (not only transcription) of nitric oxide synthesis genes through p38 and eIF5A hypusination pathway, representing a dual transcriptional and translational control mechanism. Mincle-deficient macrophages, TLR/Mincle stimulation assays, p38 inhibition, eIF5A hypusination analysis, NO production assays Nature communications Medium 27089465
2016 Mincle/Syk/Card9 signaling axis is essential for experimental autoimmune uveoretinitis (EAU); Mincle deletion or Card9 deletion prevents Th17 polarization and disease, and Mincle activation alone is sufficient to generate the EAU phenotype. Mincle-/-, Card9-/-, Dectin-1-/-, Dectin-2-/- mice in EAU model, direct Mincle agonist injection, Syk inhibition Journal of immunology High 26921309
2017 β-Glucosylceramide (GlcCer), a ubiquitous intracellular metabolite, is an endogenous Mincle ligand released upon cell damage; identified by fractionation, MS, and NMR; GBA1 (β-glucosylceramidase)-deficient cells accumulate GlcCer and trigger enhanced Mincle-dependent antigen-specific T-cell responses. Biochemical fractionation of dead cell supernatants, MS and NMR structural identification, synthetic GlcCer activation assays, Mincle-deficient macrophages, GBA1×Mincle double-KO mice, DC antigen presentation assays Proceedings of the National Academy of Sciences of the United States of America High 28373578
2017 Mincle recognition of cholesterol sulfate from barrier epithelium drives sterile inflammation; subcutaneous injection of cholesterol sulfate causes Mincle-dependent local inflammatory response; Mincle-deficient mice show significantly suppressed allergic contact dermatitis. Reporter cell assays with Mincle, Mincle-/- mice in allergic contact dermatitis model, cholesterol sulfate ligand specificity assays Proceedings of the National Academy of Sciences of the United States of America Medium 28292894
2017 CD11b negatively regulates Mincle signaling by forming a Mincle-CD11b complex upon Mincle activation; CD11b recruits Lyn, SIRPα, and SHP1 which dephosphorylate Syk to dampen Mincle-mediated inflammation. CD11b-deficient macrophages (hyperinflammation phenotype), co-immunoprecipitation of Mincle-CD11b complex, Lyn activator (MLR1023) functional experiments, phospho-Syk assays Experimental & molecular medicine Medium 29400702
2017 TDM-coated beads recruit Mincle during FcγR-mediated phagocytosis and interfere with phagosome maturation through Mincle-dependent recruitment of SHP-1 and inhibitory FcγRIIB signaling. IgG-opsonized TDM bead phagocytosis assays, SHP-1 and FcγRIIB functional analyses, phagosome maturation assays PloS one Medium 28384255
2017 Mincle recognizes the glycolipid Glc-DAG (glucosyl-diacylglycerol) of Streptococcus pneumoniae; Mincle-deficient mice show increased bacterial loads, decreased survival, and dysregulated cytokine responses in pneumococcal pneumonia. Mincle reporter cell activation with purified Glc-DAG, Mincle-/- macrophage cytokine assays, Mincle-KO mouse pneumonia model, hematopoietic reconstitution experiments PLoS pathogens High 27923071
2017 Mincle mediates NET (neutrophil extracellular trap) formation through autophagy activation; Mincle-/- neutrophils show impaired autophagy and NET formation in vitro and in vivo during Klebsiella pneumoniae infection, while ROS production remains intact; autophagy induction rescues NET formation in Mincle-/- neutrophils. Mincle-/- neutrophils stimulated in vitro and in vivo Klebsiella infection, NET formation assays, ROS assays, autophagy activation analysis, tamoxifen (autophagy inducer) rescue experiment The Journal of infectious diseases Medium 28186242
2017 Mincle fine structure of fatty acids is critical for glycolipid binding to its CRD; glucose and mannose esterified at O-6 by a synthetic α-branched 32-carbon fatty acid show agonist activity similar to TDM; Mincle-dependent cytokine production confirmed with primary human and murine cells. Chemical synthesis, molecular dynamics simulations, protein mutagenesis, reporter cell assays, Mincle-/- primary cell cytokine assays, in vivo immunization Proceedings of the National Academy of Sciences of the United States of America High 28223515
2018 Mincle recognizes the lipoteichoic acid anchor monoglucosyldiacylglycerol (MGDG) of Group A Streptococcus via the CARD9 pathway to drive protective antibacterial immunity; Mincle-deficient mice show impaired cytokine production, severe bacteremia, and rapid lethality upon GAS infection. Gene expression analysis of CARD9-pathway contribution, purified MGDG reporter cell assays, Mincle-/- mouse GAS infection model Proceedings of the National Academy of Sciences of the United States of America High 30352847
2019 The Mincle-Syk signaling axis in dendritic cells in Peyer's patches senses mucosal-resident commensals and triggers IL-6 and IL-23p19 expression to regulate intestinal Th17 cell and ILC3 function; Mincle-deficient mice show impaired RegIIIγ and IgA production and increased systemic translocation of gut microbiota, with consequent liver inflammation. Mincle-/- mice, conditional Syk KO in CD11c+ cells, intestinal cytokine and IgA assays, microbiota translocation assays, liver inflammation analysis Immunity High 30709742
2019 CLEC4E activation in combination with TLR4 induces autophagy in macrophages through MYD88 and PtdIns3K pathways, leading to lysosome biogenesis and enhanced intracellular killing of Mycobacterium tuberculosis; autophagy-deficient (Atg5-KO, Becn1-KD) macrophages show elevated Mtb survival. CLEC4E+TLR4 agonist co-stimulation, autophagy-deficient macrophages, lysosome biogenesis assays, intracellular Mtb killing assays in mice and guinea pigs Autophagy Medium 31462144
2020 β-Glucosylceramide in combination with free cholesterol acts as an endogenous Mincle ligand to trigger sustained inflammation after acute kidney injury; free cholesterol markedly enhances the agonistic effect of β-GlcCer on Mincle; Mincle-deficient mice are protected from kidney damage after ischemia-reperfusion injury. Lipophilic extract fractionation from injured kidney, Mincle reporter assays, Mincle-/- mouse ischemia-reperfusion model, histological analysis of β-GlcCer and free cholesterol accumulation near Mincle-expressing macrophages The Journal of experimental medicine High 32797195
2020 Mincle/Syk/NF-κB signaling is essential for maintaining protumoral M2-like tumor-associated macrophage (TAM) function; Mincle silencing in TAM promotes M1-like phenotype in vitro; ultrasound microbubble-mediated tumor-specific Mincle silencing suppresses TAM-driven cancer progression in syngeneic mouse cancer models. Single-cell RNA sequencing, Mincle siRNA in BMDMs, adoptive transfer of Mincle-silenced BMDMs into NOD/SCID mice, ultrasound microbubble gene delivery in syngeneic LLC and B16F10 models, Syk phosphorylation assays Cancer immunology research High 32532809
2020 Mincle/Syk signaling in macrophages promotes intestinal mucosal inflammation (Crohn's disease model) by inducing macrophage pyroptosis and MAPK-driven chemokine production to recruit neutrophils; Mincle-/- mice and Syk-inhibitor-treated mice show reduced colitis. Mincle-/- mice in colitis model, Syk inhibitor, Mincle agonist (TDB) in vivo, BMDMs from Mincle-/- mice, pyroptosis and cytokine assays Journal of Crohn's & colitis Medium 32333776
2021 SAP130 released from damaged renal tubular cells activates macrophage Mincle to drive necroinflammation; Mincle expression is negatively regulated post-transcriptionally by miR-219c-3p binding to Mincle 3'-UTR; lentivirus-mediated overexpression of miR-219c-3p blunts Mincle expression and macrophage infiltration in AKI. Luciferase 3'-UTR reporter assay (miR-219c binding to Mincle), lentiviral miR-219c overexpression in vivo, recombinant SAP130 administration in Mincle-/- mice, UUO and cisplatin AKI models Cell death & disease High 34556635
2021 Clec4e (Mincle) is expressed in cardiac vasculature, myocytes, and infiltrating leukocytes after myocardial ischemia-reperfusion injury; loss of Clec4e reduces acute cardiac injury, neutrophil infiltration, infarct size, and improves LV structural and functional remodeling at 4 weeks. Clec4e-/- mice in myocardial ischemia-reperfusion model, porcine and human myocardial samples for expression analysis, early transcriptome analysis of LV tissue JACC. Basic to translational science Medium 34466750
2022 Mincle has a T cell-intrinsic role in TH17-mediated CNS inflammation: TH17 cells express Mincle, and β-glucosylceramide released by dying cells engages Mincle on TH17 cells to activate the ASC-NLRP3 inflammasome, triggering Caspase8-dependent IL-1β production that drives TH17 proliferation through an autocrine loop. T cell-specific Mincle deletion in EAE model, Mincle expression profiling in TH17 vs TH1, β-GlcCer stimulation assays, NLRP3/ASC/Caspase8 pathway analysis, β-GlcCer synthesis inhibitor in vivo Nature communications High 35504893
2023 Peroxiredoxin 1 (Prdx1) is a novel DAMP that directly interacts with Mincle on macrophages to activate Mincle/Syk/NF-κB signaling and drive M1 polarization; Prdx1 knockout or neutralization protects against AKI, and this protection is reversed by recombinant Prdx1; Mincle knockdown abolishes rPrdx1-induced Syk activation. Prdx1-/- mice, Prdx1-neutralizing antibody, recombinant Prdx1 protein, co-immunoprecipitation (Prdx1-Mincle interaction), Mincle knockdown, primary peritoneal macrophage assays Kidney international High 37164261
2023 Macrophages mediate psoriasis via the Mincle-Syk-NF-κB signaling pathway; LPS induces Mincle expression in M1 macrophages via a PU.1-dependent transcriptional mechanism; adoptive transfer of Mincle-KO macrophages fails to restore psoriasis, and Mincle-neutralizing antibody significantly improves psoriasis in mice. Macrophage depletion + adoptive transfer, macrophage-specific Mincle KO mice (Mincleloxp/Lyz2-cre), PU.1 ChIP or binding assay, Mincle-neutralizing antibody in vivo Cell death discovery High 37117184
2025 Mincle (Clec4e) is essential for Enterococcus faecalis-induced trained immunity in bone marrow progenitors following intestinal barrier disruption; Clec4e-/- mice show impaired trained immunity upon E. faecalis administration and reduced colitis pathology after DSS treatment. Clec4e-/- mice, DSS gut permeability model, heat-killed E. faecalis stimulation of bone marrow progenitors, in vitro and in vivo trained immunity readouts Immunity Medium 39848243

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 Direct recognition of the mycobacterial glycolipid, trehalose dimycolate, by C-type lectin Mincle. The Journal of experimental medicine 616 20008526
2008 Mincle is an ITAM-coupled activating receptor that senses damaged cells. Nature immunology 571 18776906
2016 The necrosome promotes pancreatic oncogenesis via CXCL1 and Mincle-induced immune suppression. Nature 523 27049944
2010 Cutting edge: Mincle is essential for recognition and adjuvanticity of the mycobacterial cord factor and its synthetic analog trehalose-dibehenate. Journal of immunology (Baltimore, Md. : 1950) 390 20164423
2009 C-type lectin Mincle is an activating receptor for pathogenic fungus, Malassezia. Proceedings of the National Academy of Sciences of the United States of America 344 19171887
2019 Microbiota Sensing by Mincle-Syk Axis in Dendritic Cells Regulates Interleukin-17 and -22 Production and Promotes Intestinal Barrier Integrity. Immunity 188 30709742
2016 The pattern recognition receptor, Mincle, is essential for maintaining the M1 macrophage phenotype in acute renal inflammation. Kidney international 148 28017324
2017 Intracellular metabolite β-glucosylceramide is an endogenous Mincle ligand possessing immunostimulatory activity. Proceedings of the National Academy of Sciences of the United States of America 141 28373578
2013 Structural analysis for glycolipid recognition by the C-type lectins Mincle and MCL. Proceedings of the National Academy of Sciences of the United States of America 133 24101491
2013 The Mincle-activating adjuvant TDB induces MyD88-dependent Th1 and Th17 responses through IL-1R signaling. PloS one 119 23308247
2012 Neutrophils Promote Mycobacterial Trehalose Dimycolate-Induced Lung Inflammation via the Mincle Pathway. PLoS pathogens 118 22496642
2014 Fungal engagement of the C-type lectin mincle suppresses dectin-1-induced antifungal immunity. Cell host & microbe 114 24721577
2014 MCL and Mincle: C-Type Lectin Receptors That Sense Damaged Self and Pathogen-Associated Molecular Patterns. Frontiers in immunology 111 25002863
2015 Human Mincle Binds to Cholesterol Crystals and Triggers Innate Immune Responses. The Journal of biological chemistry 109 26296894
2013 Mechanism for recognition of an unusual mycobacterial glycolipid by the macrophage receptor mincle. The Journal of biological chemistry 104 23960080
2014 C-type lectin receptor dectin-3 mediates trehalose 6,6'-dimycolate (TDM)-induced Mincle expression through CARD9/Bcl10/MALT1-dependent nuclear factor (NF)-κB activation. The Journal of biological chemistry 103 25202022
2020 Isoliquiritigenin Attenuates UUO-Induced Renal Inflammation and Fibrosis by Inhibiting Mincle/Syk/NF-Kappa B Signaling Pathway. Drug design, development and therapy 102 32341639
2019 Quercetin protects against cisplatin-induced acute kidney injury by inhibiting Mincle/Syk/NF-κB signaling maintained macrophage inflammation. Phytotherapy research : PTR 102 31497913
2018 Curcumin relieved cisplatin-induced kidney inflammation through inhibiting Mincle-maintained M1 macrophage phenotype. Phytomedicine : international journal of phytotherapy and phytopharmacology 99 30599909
2015 C-Type Lectin Receptor MCL Facilitates Mincle Expression and Signaling through Complex Formation. Journal of immunology (Baltimore, Md. : 1950) 97 25888641
2017 Rational design of adjuvants targeting the C-type lectin Mincle. Proceedings of the National Academy of Sciences of the United States of America 92 28223515
2013 Mincle, the receptor for mycobacterial cord factor, forms a functional receptor complex with MCL and FcεRI-γ. European journal of immunology 91 23921530
2016 Human albumin attenuates excessive innate immunity via inhibition of microglial Mincle/Syk signaling in subarachnoid hemorrhage. Brain, behavior, and immunity 90 27845194
2016 Age-Specific Adjuvant Synergy: Dual TLR7/8 and Mincle Activation of Human Newborn Dendritic Cells Enables Th1 Polarization. Journal of immunology (Baltimore, Md. : 1950) 85 27793997
2019 Gut Microbiota Regulates Mincle Mediated Activation of Lung Dendritic Cells to Protect Against Mycobacterium tuberculosis. Frontiers in immunology 83 31231363
2016 Leishmania Uses Mincle to Target an Inhibitory ITAM Signaling Pathway in Dendritic Cells that Dampens Adaptive Immunity to Infection. Immunity 83 27742545
2015 Contribution of MINCLE-SYK Signaling to Activation of Primary Human APCs by Mycobacterial Cord Factor and the Novel Adjuvant TDB. Journal of immunology (Baltimore, Md. : 1950) 82 26202982
2008 Human and mouse macrophage-inducible C-type lectin (Mincle) bind Candida albicans. Glycobiology 80 18509109
2018 Mincle: 20 years of a versatile sensor of insults. International immunology 78 29726997
2017 Receptor Mincle promotes skin allergies and is capable of recognizing cholesterol sulfate. Proceedings of the National Academy of Sciences of the United States of America 75 28292894
2016 Necrotic Cell Sensor Clec4e Promotes a Proatherogenic Macrophage Phenotype Through Activation of the Unfolded Protein Response. Circulation 71 27587433
2013 Involvement of Mincle and Syk in the changes to innate immunity after ischemic stroke. Scientific reports 71 24212132
2019 Induction of autophagy through CLEC4E in combination with TLR4: an innovative strategy to restrict the survival of Mycobacterium tuberculosis. Autophagy 70 31462144
2023 Peroxiredoxin 1 aggravates acute kidney injury by promoting inflammation through Mincle/Syk/NF-κB signaling. Kidney international 69 37164261
2016 IRAKM-Mincle axis links cell death to inflammation: Pathophysiological implications for chronic alcoholic liver disease. Hepatology (Baltimore, Md.) 63 27628766
2012 Mincle is not essential for controlling Mycobacterium tuberculosis infection. Immunobiology 62 22784441
2012 Role of Mincle in alveolar macrophage-dependent innate immunity against mycobacterial infections in mice. Journal of immunology (Baltimore, Md. : 1950) 62 22869905
2020 The Mincle/Syk/NF-κB Signaling Circuit Is Essential for Maintaining the Protumoral Activities of Tumor-Associated Macrophages. Cancer immunology research 61 32532809
2017 Sensing Lipids with Mincle: Structure and Function. Frontiers in immunology 61 29230225
2016 C-type Lectin Mincle Recognizes Glucosyl-diacylglycerol of Streptococcus pneumoniae and Plays a Protective Role in Pneumococcal Pneumonia. PLoS pathogens 60 27923071
2014 Differential control of Mincle-dependent cord factor recognition and macrophage responses by the transcription factors C/EBPβ and HIF1α. Journal of immunology (Baltimore, Md. : 1950) 58 25156364
2016 Mincle Activation and the Syk/Card9 Signaling Axis Are Central to the Development of Autoimmune Disease of the Eye. Journal of immunology (Baltimore, Md. : 1950) 57 26921309
2016 Mincle-mediated translational regulation is required for strong nitric oxide production and inflammation resolution. Nature communications 56 27089465
2014 Mincle signaling in the innate immune response after traumatic brain injury. Journal of neurotrauma 54 25111533
2013 Recognition of the mycobacterial cord factor by Mincle: relevance for granuloma formation and resistance to tuberculosis. Frontiers in immunology 54 23355839
2020 C-type lectin Mincle mediates cell death-triggered inflammation in acute kidney injury. The Journal of experimental medicine 52 32797195
2012 Mincle polarizes human monocyte and neutrophil responses to Candida albicans. Immunology and cell biology 52 22641025
2017 Mincle-Mediated Neutrophil Extracellular Trap Formation by Regulation of Autophagy. The Journal of infectious diseases 50 28186242
2015 Fonsecaea pedrosoi-induced Th17-cell differentiation in mice is fostered by Dectin-2 and suppressed by Mincle recognition. European journal of immunology 50 26140582
2020 Mincle/Syk Signalling Promotes Intestinal Mucosal Inflammation Through Induction of Macrophage Pyroptosis in Crohn's Disease. Journal of Crohn's & colitis 46 32333776
2015 Corynomycolic acid-containing glycolipids signal through the pattern recognition receptor Mincle. Chemical communications (Cambridge, England) 45 25714652
2015 Induction of Mincle by Helicobacter pylori and consequent anti-inflammatory signaling denote a bacterial survival strategy. Scientific reports 45 26456705
2017 The Interaction of Pneumocystis with the C-Type Lectin Receptor Mincle Exerts a Significant Role in Host Defense against Infection. Journal of immunology (Baltimore, Md. : 1950) 44 28298521
2014 Defining the conformation of human mincle that interacts with mycobacterial trehalose dimycolate. Glycobiology 43 25028392
2018 Lipoteichoic acid anchor triggers Mincle to drive protective immunity against invasive group A Streptococcus infection. Proceedings of the National Academy of Sciences of the United States of America 42 30352847
2015 The C-type lectin receptor Mincle binds to Streptococcus pneumoniae but plays a limited role in the anti-pneumococcal innate immune response. PloS one 42 25658823
2015 Mycobacterial receptor, Clec4d (CLECSF8, MCL), is coregulated with Mincle and upregulated on mouse myeloid cells following microbial challenge. European journal of immunology 41 26558717
2021 Artesunate relieves acute kidney injury through inhibiting macrophagic Mincle-mediated necroptosis and inflammation to tubular epithelial cell. Journal of cellular and molecular medicine 40 34337860
2016 Trehalose diester glycolipids are superior to the monoesters in binding to Mincle, activation of macrophages in vitro and adjuvant activity in vivo. Innate immunity 40 27252171
2016 An atypical role for the myeloid receptor Mincle in central nervous system injury. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 40 27492949
2017 M1 macrophage triggered by Mincle leads to a deterioration of acute kidney injury. Kidney international 39 28202166
2017 The Mincle ligand trehalose dibehenate differentially modulates M1-like and M2-like macrophage phenotype and function via Syk signaling. Immunity, inflammation and disease 39 28722316
2016 Mincle Signaling Promotes Con A Hepatitis. Journal of immunology (Baltimore, Md. : 1950) 38 27559045
2014 Macrophage-inducible C-type lectin Mincle-expressing dendritic cells contribute to control of splenic Mycobacterium bovis BCG infection in mice. Infection and immunity 38 25332121
2010 Self and nonself recognition through C-type lectin receptor, Mincle. Self/nonself 38 21487505
2021 BAY61‑3606 attenuates neuroinflammation and neurofunctional damage by inhibiting microglial Mincle/Syk signaling response after traumatic brain injury. International journal of molecular medicine 37 34751408
2018 Microglial Mincle receptor in the PVN contributes to sympathetic hyperactivity in acute myocardial infarction rat. Journal of cellular and molecular medicine 37 30353660
2017 Trehalose dimycolate interferes with FcγR-mediated phagosome maturation through Mincle, SHP-1 and FcγRIIB signalling. PloS one 37 28384255
2016 Mincle-mediated anti-inflammatory IL-10 response counter-regulates IL-12 in vitro. Innate immunity 36 26939595
2021 SAP130 released by damaged tubule drives necroinflammation via miRNA-219c/Mincle signaling in acute kidney injury. Cell death & disease 35 34556635
2017 Toll-Like Receptor 2 and Mincle Cooperatively Sense Corynebacterial Cell Wall Glycolipids. Infection and immunity 35 28483856
2021 Clec4e-Receptor Signaling in Myocardial Repair After Ischemia-Reperfusion Injury. JACC. Basic to translational science 33 34466750
2020 Astragalus propinquus Schischkin and Panax notoginseng (A&P) compound relieved cisplatin-induced acute kidney injury through inhibiting the mincle maintained macrophage inflammation. Journal of ethnopharmacology 33 32004631
2024 SAP130 released by ferroptosis tubular epithelial cells promotes macrophage polarization via Mincle signaling in sepsis acute kidney injury. International immunopharmacology 32 38320352
2019 The CARD9-Associated C-Type Lectin, Mincle, Recognizes La Crosse Virus (LACV) but Plays a Limited Role in Early Antiviral Responses against LACV. Viruses 31 30917612
2017 Macrophage inducible C-type lectin (Mincle) recognizes glycosylated surface (S)-layer of the periodontal pathogen Tannerella forsythia. PloS one 31 28264048
2019 Mincle and STING-Stimulating Adjuvants Elicit Robust Cellular Immunity and Drive Long-Lasting Memory Responses in a Foot-and-Mouth Disease Vaccine. Frontiers in immunology 30 31736952
2021 S-Layer From Lactobacillus brevis Modulates Antigen-Presenting Cell Functions via the Mincle-Syk-Card9 Axis. Frontiers in immunology 29 33732234
2019 The pattern recognition receptors dectin-2, mincle, and FcRγ impact the dynamics of phagocytosis of Candida, Saccharomyces, Malassezia, and Mucor species. PloS one 29 31393930
2022 TH17 cells promote CNS inflammation by sensing danger signals via Mincle. Nature communications 28 35504893
2020 C-type lectin receptors Mcl and Mincle control development of multiple sclerosis-like neuroinflammation. The Journal of clinical investigation 28 31725411
2008 Sensing necrosis with Mincle. Nature immunology 28 18800160
2018 CD209a Synergizes with Dectin-2 and Mincle to Drive Severe Th17 Cell-Mediated Schistosome Egg-Induced Immunopathology. Cell reports 27 29386115
2012 Mincle and human B cell function. Journal of autoimmunity 27 22698596
2018 The Mycobacterial Adjuvant Analogue TDB Attenuates Neuroinflammation via Mincle-Independent PLC-γ1/PKC/ERK Signaling and Microglial Polarization. Molecular neurobiology 26 29876879
2017 Mincle inhibits neutrophils and macrophages apoptosis in A. fumigatus keratitis. International immunopharmacology 26 28888778
2016 Signalling through MyD88 drives surface expression of the mycobacterial receptors MCL (Clecsf8, Clec4d) and Mincle (Clec4e) following microbial stimulation. Microbes and infection 26 27005451
2012 Silencing of renal DNaseI in murine lupus nephritis imposes exposure of large chromatin fragments and activation of Toll like receptors and the Clec4e. PloS one 26 22479529
2023 Macrophages mediate psoriasis via Mincle-dependent mechanism in mice. Cell death discovery 25 37117184
2018 Synthesis of Branched Trehalose Glycolipids and Their Mincle Agonist Activity. The Journal of organic chemistry 25 29781274
2019 S-Layer Glycoprotein From Lactobacillus kefiri Exerts Its Immunostimulatory Activity Through Glycan Recognition by Mincle. Frontiers in immunology 23 31297112
2018 Integrin CD11b negatively regulates Mincle-induced signaling via the Lyn-SIRPα-SHP1 complex. Experimental & molecular medicine 23 29400702
2025 Microbiota translocation following intestinal barrier disruption promotes Mincle-mediated training of myeloid progenitors in the bone marrow. Immunity 22 39848243
2019 Species-Specific Structural Requirements of Alpha-Branched Trehalose Diester Mincle Agonists. Frontiers in immunology 22 30873180
2018 Targeting the Mincle and TLR3 receptor using the dual agonist cationic adjuvant formulation 9 (CAF09) induces humoral and polyfunctional memory T cell responses in calves. PloS one 22 30063728
2017 Immune transcriptome reveals the mincle C-type lectin receptor acts as a partial replacement for TLR4 in lipopolysaccharide-mediated inflammatory response in barramundi (Lates calcarifer). Molecular immunology 22 28095348
2016 Stat6-Dependent Inhibition of Mincle Expression in Mouse and Human Antigen-Presenting Cells by the Th2 Cytokine IL-4. Frontiers in immunology 22 27790218
2021 Orientia tsutsugamushi selectively stimulates the C-type lectin receptor Mincle and type 1-skewed proinflammatory immune responses. PLoS pathogens 21 34320039
2020 6,6'-Aryl trehalose analogs as potential Mincle ligands. Bioorganic & medicinal chemistry 20 32616186
2015 Mouse mincle: characterization as a model for human mincle and evolutionary implications. Molecules (Basel, Switzerland) 20 25884549

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