Affinage

CLEC7A

C-type lectin domain family 7 member A · UniProt Q9BXN2

Length
247 aa
Mass
27.6 kDa
Annotated
2026-06-09
100 papers in source corpus 37 papers cited in narrative 37 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CLEC7A (Dectin-1) is a type II transmembrane C-type lectin-like receptor that serves as the principal non-opsonic pattern-recognition receptor for fungal beta-(1,3/1,6)-glucans on myeloid cells, coupling ligand recognition to phagocytosis, inflammasome activation, cytokine output, and host antifungal defense (PMID:12163569, PMID:16341139). Ligand binding drives receptor dimerization/oligomerization into nanoscale clusters whose agonistic potential is set by glucan quaternary structure rather than affinity (PMID:37515324); clustering triggers Src-kinase phosphorylation of the cytoplasmic ITAM-like motif and recruitment/activation of Syk (PMID:23609446), which acts through PKCdelta (PMID:21653233) and the CARD9-NF-kappaB axis to drive pro-inflammatory transcription (PMID:21677049). Downstream, Dectin-1/Syk signaling controls intraphagosomal acidification and phagolysosomal maturation, including the trafficking of TLR9 to glucan-containing phagosomes (PMID:23609446, PMID:26829985), activates the NLRP3 inflammasome for IL-1beta secretion via cathepsin B, ROS, and potassium efflux (PMID:20421639), and engages CARD9-bridged RIPK1-RIPK3-MLKL necroptosis and unconventional autophagy-dependent secretion during fungal infection (PMID:30944411, PMID:24808366). A parallel Syk-independent, SFK-dependent RHOA-ROCK-MLC branch generates the mechanical force required for phagocytosis (PMID:31964711). Receptor output is shaped by the intracellular domain, which determines species-specific sensitivity to low-valency glucans (PMID:28848046), by MS4A4A co-localization in lipid rafts (PMID:31263276), by nanoscale proximity to TLR2 for signaling synergy (PMID:31754039), and by isoform-specific proteolytic cleavage (PMID:29401615). Biallelic CLEC7A mutations cause human Dectin-1 deficiency, impairing macrophage TNF-alpha and IL-1beta production against fungi in a CARD9-dependent manner (PMID:36377664). Beyond antifungal immunity, Dectin-1 recognizes endogenous ligands—galectin-3, angiotensin II, beta-amyloid, core-fucosylated IgG, galectin-9, and neuronal MD2—engaging the same Syk/NF-kappaB machinery to drive roles in thrombosis, cardiac inflammation, neuroinflammation, osteoclastogenesis, and microglial synaptic phagocytosis (PMID:35165707, PMID:36786193, PMID:37416769, PMID:33581044, PMID:36948194, PMID:39088351). Receptor abundance is transcriptionally controlled through an LTB4-BLT1-GM-CSF-PU.1 axis and by C/EBPbeta (PMID:22696442, PMID:36503542).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 2002 High

    Established which receptor accounts for non-opsonic fungal recognition, resolving whether mannose receptor, CR3, or a dedicated lectin mediates beta-glucan binding on macrophages.

    Evidence Blocking mAb (2A11), carbohydrate inhibitors, and CD11b-deficient mice in primary macrophage binding assays

    PMID:12163569

    Open questions at the time
    • Did not define the signaling output of the receptor
    • Endogenous ligands not addressed
  2. 2004 Medium

    Defined the receptor's ligand specificity for beta-1,3/1,6 glucans and revealed splice-variant heterogeneity plus an endogenous T-cell ligand, broadening its role beyond fungi.

    Evidence Glucan-particle binding assays, RT-PCR splice variant profiling, stable cell lines

    PMID:11491532 PMID:14698225

    Open questions at the time
    • Identity of the endogenous T-cell ligand not determined
    • Functional consequence of isoform differences not resolved
  3. 2006 High

    Showed full-length and stalkless isoforms are functionally distinct, establishing that the stalk region tunes binding and cytokine output.

    Evidence Stable transfectants (NIH-3T3, RAW264.7), zymosan binding/phagocytosis and cytokine assays; cytoplasmic isoform localization and RanBPM interaction by Y2H/GST pulldown/Co-IP

    PMID:16622020 PMID:16870151

    Open questions at the time
    • Physiological role of cytoplasmic isoform-RanBPM interaction unclear
    • In vivo relevance of isoform ratios not tested
  4. 2006 High

    Defined the core signaling logic: an ITAM-like cytoplasmic motif coupling to Syk to drive phagocytosis, cytokines, and respiratory burst, with TLR collaboration.

    Evidence Review synthesizing Syk inhibitor, mutant, and cellular functional data across labs

    PMID:16341139

    Open questions at the time
    • Did not place individual downstream effectors in order
    • Spatial requirements of TLR collaboration unaddressed
  5. 2010 High

    Ordered the IL-1beta arm, separating Syk-dependent transcription from inflammasome-dependent secretion and identifying the upstream requirements for NLRP3 activation.

    Evidence RNAi of Dectin-1/Syk/NLRP3, phagocytosis and cathepsin B/ROS inhibitors in human macrophages

    PMID:20421639

    Open questions at the time
    • Direct molecular link from Syk to NLRP3 not defined
    • Relative contribution in vivo not tested
  6. 2011 High

    Identified PKCdelta as a required node controlling Syk/Src recruitment to the receptor, refining the proximal signaling hierarchy.

    Evidence Co-IP for direct binding, siRNA, NADPH oxidase and phagocytosis assays in primary human monocytes

    PMID:21653233

    Open questions at the time
    • Structural basis of Dectin-1-PKCdelta binding unknown
    • Whether PKCdelta acts in all cell types unclear
  7. 2011 High

    Placed Dectin-1 within the broader CLR signaling framework relative to FcRgamma-coupled Dectin-2, converging on CARD9-NF-kappaB.

    Evidence Knockout models and cytokine assays across fungi

    PMID:21677049

    Open questions at the time
    • Did not address non-CARD9 branches
    • Endogenous-ligand signaling not covered
  8. 2013 High

    Demonstrated Src-mediated phosphorylation precedes Syk and that Syk activity is required for phagolysosomal maturation, linking receptor signaling to phagosome biology.

    Evidence GFP-Dectin-1 live imaging, Src/Syk inhibitors, signaling-dead mutant, LAMP-1/Rab5B/acidification assays

    PMID:23609446

    Open questions at the time
    • Effectors connecting Syk to maturation machinery not defined
  9. 2016 High

    Extended phagosome control to TLR9 trafficking, establishing that Dectin-1/Syk coordinates a second innate sensor for antifungal gene expression.

    Evidence Syk and acidification inhibitors, TLR9 live imaging, gene expression in macrophages

    PMID:26829985

    Open questions at the time
    • Molecular trafficking machinery for TLR9 unresolved
  10. 2014 Medium

    Linked Dectin-1/Syk to autophagy-dependent unconventional secretion, broadening its output beyond classical cytokine release.

    Evidence Transcriptome/secretome analysis with autophagy and inflammasome inhibitors in human macrophages

    PMID:24808366

    Open questions at the time
    • Specific secreted cargo set not fully defined
    • Mechanism of autophagy engagement unclear
  11. 2017 High

    Showed the intracellular—not the ligand-binding—domain sets species-specific sensitivity, pinpointing two residues that govern low-valency glucan reactivity.

    Evidence Reciprocal human/mouse domain mutagenesis, reporter and DC gene expression assays

    PMID:28848046

    Open questions at the time
    • Mechanism by which intracellular residues alter ligand sensitivity unclear
  12. 2019 High

    Defined modulators of receptor function: MS4A4A lipid-raft partnering and a nanoscale Dectin-1-TLR2 proximity threshold required for signaling synergy.

    Evidence Co-IP/lipid raft fractionation and Ms4a4a-KO mice; spatially patterned ligand particles and super-resolution microscopy

    PMID:31263276 PMID:31754039

    Open questions at the time
    • Molecular basis of MS4A4A-Dectin-1 interaction not resolved
    • How proximity converts to biochemical synergy unclear
  13. 2023 Medium

    Established the biophysical basis of activation: ligand-induced multimerization driven by glucan quaternary structure, not affinity, producing small receptor clusters at fungal contacts.

    Evidence Fluorescence diffusion/aggregation, glucan denaturation, live-cell imaging at fungal contact sites

    PMID:37515324

    Open questions at the time
    • Structural model of the cluster not determined
    • Link from cluster size to signaling strength not quantified
  14. 2019 High

    Revealed Dectin-1 as a receptor for endogenous galectin-3 on platelets and for core-fucosylated IgG, expanding ligand repertoire beyond microbial glucans.

    Evidence Dectin-1-/- mice, laminarin, platelet/thrombosis assays; SPR/NMR and glycan-array binding for IgG core fucose

    PMID:31625659 PMID:35165707

    Open questions at the time
    • Structural detail of IgG recognition limited
    • In vivo relevance of fucose recognition not established
  15. 2023 High

    Identified angiotensin II and beta-amyloid as direct agonists that drive Dectin-1 homodimerization and Syk/NF-kappaB signaling, linking the receptor to cardiac inflammation and Alzheimer pathology.

    Evidence Binding studies, site-directed mutagenesis (R184), Dectin-1-KO mice, bone marrow chimeras, microglial siRNA, behavioral testing

    PMID:36786193 PMID:37416769

    Open questions at the time
    • Whether glucan and non-glucan ligands use the same binding surface unresolved for Abeta42
    • Therapeutic targetability not established
  16. 2022 High

    Validated CLEC7A loss as a human inborn susceptibility, confirming the CARD9-dependent cytokine-killing axis is conserved across species.

    Evidence Patient PBMC assays plus Dectin-1-/- and CARD9-/- mouse macrophages and infection model

    PMID:36377664

    Open questions at the time
    • Full clinical spectrum of human deficiency not defined
  17. 2022 High

    Showed Dectin-1 acts as a co-inhibitory checkpoint by promoting productive FcgammaRIIb conformations, controlling IgG-dependent reprogramming of osteoclastogenesis.

    Evidence Dectin-1-/- and FcgammaRIIb-/- mice, atomistic MD simulations, super-resolution microscopy, osteoclastogenesis assays

    PMID:36948194

    Open questions at the time
    • Physical interaction surface with FcgammaRIIb not crystallographically resolved
  18. 2024 Medium

    Extended endogenous-ligand signaling to a microglial Clec7a-MD2 interaction governing synaptic phagocytosis after stroke and to cell-intrinsic C5a-C5aR1 amplification of antifungal effector function.

    Evidence Microglial RNA-seq, Co-IP, Clec7a gain/loss in stroke; primary macrophage C5aR1 inhibitors, mtROS and fungal killing assays

    PMID:38252818 PMID:39088351

    Open questions at the time
    • Direct Clec7a-MD2 binding interface unresolved
    • Source/regulation of cell-intrinsic C5a unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single receptor discriminates among structurally unrelated agonists (glucans, galectins, Ang II, Abeta42, IgG, MD2) to select distinct downstream programs (CARD9-dependent vs NFAT-dependent vs RHOA-ROCK) remains unresolved.
  • No structure of a ligand-bound Dectin-1 cluster
  • Rules governing CARD9-dependent vs CARD9-independent branch selection unknown
  • Integration of conflicting pro- and anti-inflammatory outputs in vivo unclear

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0001618 virus receptor activity 3 GO:0060089 molecular transducer activity 3 GO:0008289 lipid binding 2 GO:0140096 catalytic activity, acting on a protein 2
Localization
GO:0005886 plasma membrane 3 GO:0005829 cytosol 2 GO:0031410 cytoplasmic vesicle 2
Pathway
R-HSA-168256 Immune System 4 R-HSA-162582 Signal Transduction 3 R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-5357801 Programmed Cell Death 2
Partners
CARD9FCGR2BLGALS3MS4A4APRKCDRANBP9SYKTLR2
Complex memberships
Dectin-1-MS4A4A lipid raft complex

Evidence

Reading pass · 37 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 Dectin-1 is the major beta-glucan receptor on macrophages responsible for non-opsonic recognition of zymosan; blocking with anti-Dectin-1 mAb (2A11) or genetic CD11b deficiency demonstrated that Dectin-1 (not MR or CR3) mediates beta-glucan-dependent zymosan binding by primary macrophages. Blocking monoclonal antibody (2A11), carbohydrate inhibitors, genetic CD11b-deficient mice, primary macrophage binding assays The Journal of experimental medicine High 12163569
2004 Murine Dectin-1, a type II C-type lectin-like receptor, non-opsonically recognizes beta-1,3 and beta-1,6 linked glucan-rich particles and intact yeast; human Dectin-1 is functionally similar but exists as two major splice variants differentially expressed in leukocyte populations. Dectin-1 also recognizes an endogenous ligand on T cells. Binding assays with purified glucan particles, RT-PCR for splice variant expression, stable cell line expression Molecular immunology Medium 14698225
2001 Human DECTIN-1 (CLECSF12) encodes a type II transmembrane glycoprotein with a C-type lectin-like domain, maps to the NK gene complex on chromosome 12p12.3-p13.2, and is expressed as two alternatively spliced forms preferentially in dendritic cells. cDNA cloning, RT-PCR expression profiling, chromosomal mapping Immunogenetics Medium 11491532
2006 Mice express at least two functionally distinct splice isoforms of Dectin-1 (full-length Dectin-1A and stalkless Dectin-1B); Dectin-1B shows significantly reduced binding at lower temperatures and differential TNF-alpha induction compared to Dectin-1A in RAW264.7 macrophages. Equivalent human isoforms share these properties. RT-PCR identification of splice forms, stable expression in NIH-3T3 and RAW264.7 cell lines, zymosan binding and phagocytosis assays, cytokine measurement Journal of immunology High 16622020
2002 Human Dectin-1b splice variant expressed in HeLa cells acts as a co-stimulatory molecule, upregulating T lymphocyte activation markers, inducing IFN-gamma production, and promoting proliferation of both CD4+ and CD8+ T cells. Transfection of HeLa cells with Dectin-1b, co-culture with purified T cells, flow cytometry, cytokine ELISA Experimental hematology Medium 12423684
2006 Dectin-1 is a signalling receptor with a cytoplasmic ITAM-like motif that signals through Syk kinase, mediating phagocytosis, cytokine/chemokine production, and the respiratory burst; it can collaborate with TLRs to modulate immune responses. Review synthesizing signaling data including Syk inhibitor studies, Dectin-1 mutant analysis, and functional cellular assays from multiple labs Nature reviews. Immunology High 16341139
2010 Beta-glucans activate IL-1beta transcription via a Dectin-1/Syk-dependent pathway in human macrophages; IL-1beta secretion additionally requires phagocytosis and the cytoplasmic NLRP3 inflammasome, with lysosomal cathepsin B, ROS, and potassium efflux required for NLRP3 activation downstream of Dectin-1/Syk. RNAi knockdown of Dectin-1, Syk, NLRP3; cytochalasin D phagocytosis inhibition; cathepsin B inhibitor; pharmacologic ROS inhibitors; ELISA and RT-PCR in human macrophages Journal of immunology High 20421639
2011 Dectin-1 signals through its ITAM-like cytoplasmic motif to recruit Syk kinase upon beta-glucan binding; Dectin-2 instead signals via association with the ITAM-containing Fc receptor gamma chain; both activate the CARD9-NF-kappaB axis for pro-inflammatory cytokine gene expression. Genetic knockout models, signaling pathway analysis, cytokine production assays International immunology High 21677049
2013 Dectin-1 translocates to fungal phagosomes; upon beta-1,3-glucan recognition, Dectin-1 undergoes tyrosine phosphorylation by Src kinases with subsequent Syk activation; Syk activation regulates intraphagosomal pH and phagolysosomal maturation (LAMP-1 acquisition, Rab5B clearance). A signaling-incompetent Dectin-1 mutant failed to support phagosome maturation. GFP-Dectin-1 live cell imaging, pharmacologic Src/Syk inhibitors, signaling-incompetent Dectin-1 mutant expression, phagosome marker acquisition assays (LAMP-1, Rab5B), acidification assays in macrophages The Journal of biological chemistry High 23609446
2016 Dectin-1-mediated Syk activation controls trafficking of TLR9 to beta-1,3-glucan-containing phagosomes; phagosomal acidification is required for TLR9 accumulation; Dectin-1 regulates TLR9-dependent gene expression, coordinating innate antifungal defense. Pharmacological inhibition of Syk and phagosomal acidification, live-cell imaging of TLR9 trafficking, gene expression analysis in macrophages Journal of immunology High 26829985
2011 Protein kinase C-delta (PKCdelta) is a novel downstream signaling component of Dectin-1 in primary human monocytes; Syk and Src association with Dectin-1 is dependent on PKCdelta activity and expression; direct binding between Dectin-1 and PKCdelta was demonstrated. PKCdelta and Syk (but not Src) are required for Dectin-1-mediated phagocytosis. Pharmacological inhibitors, siRNA knockdown, co-immunoprecipitation (direct binding), NADPH oxidase assays, phagocytosis assays in primary human monocytes Journal of leukocyte biology High 21653233
2014 Dectin-1/Syk pathway activates both conventional and unconventional (autophagy-dependent) vesicle-mediated protein secretion in human macrophages; unconventional secretion requires inflammasome activity and active autophagy. Transcriptome and secretome analysis, bioinformatics, pharmacological inhibitors of autophagy and inflammasome, systems biology approach in human macrophages Journal of immunology Medium 24808366
2012 Macrophage dectin-1 expression is transcriptionally controlled by leukotriene B4 (LTB4) signaling through BLT1 receptor via a GM-CSF/PU.1 axis; LTB4-deficient macrophages show lower dectin-1 and PU.1 expression, and GM-CSF restores both; PU.1 siRNA abolishes LTB4-enhanced dectin-1 expression. Genetic (LT-deficient and BLT1-deficient mice), pharmacological inhibitors, siRNA knockdown of PU.1 and GM-CSF, GM-CSF rescue experiments, binding/phagocytosis/cytokine assays Journal of immunology High 22696442
2006 Human Dectin-1 isoform E (hDectin-1E) localizes to the cytoplasm (not secreted); it directly interacts with the Ran-binding protein RanBPM, with the SPRY domain of RanBPM being sufficient for interaction. Confocal microscopy (localization), yeast two-hybrid screening, GST pull-down assay (direct binding), co-immunoprecipitation Biochemical and biophysical research communications Medium 16870151
2019 MS4A4A interacts and colocalizes with Dectin-1 in lipid rafts on macrophages; Ms4a4a-deficient macrophages show defective Dectin-1 signaling and defective production of effector molecules in response to dectin-1 ligands; MS4A4A is required for dectin-1-mediated NK cell-dependent metastasis control. Co-immunoprecipitation, lipid raft fractionation, Ms4a4a knockout mice, flow cytometry, tumor metastasis models Nature immunology High 31263276
2017 The intracellular domain (not the ligand-binding domain) of human Dectin-1 determines species-specific sensitivity to low-valency beta-glucan ligands; two amino acids (Glu2 and Pro5) in the human intracellular domain confer reactivity to low-valency beta-glucan; substituting mouse-specific Lys2/Ser5 reduces this reactivity. Reciprocal mutagenesis of human and mouse Dectin-1 intracellular/extracellular domains, reporter cell activation assays, dendritic cell gene expression analysis The Journal of biological chemistry High 28848046
2023 Dectin-1A multimerization (dimerization/oligomerization) is induced by ligand binding; glucan structure (helical/quaternary conformation) determines agonistic potential by driving receptor aggregation rather than altering binding affinity; small (<15 nm) receptor clusters form at fungal contact sites proportional to exposed glucan. Fluorescence diffusion measurements, fluorescence aggregation assays, glucan denaturation experiments, live-cell imaging at fungal particle contact sites Biophysical journal Medium 37515324
2019 Galectin-3 directly binds to and activates Dectin-1 on platelets (a previously unreported Dectin-1 expression site), causing Syk phosphorylation, Ca2+ influx, PKC activation, and ROS production to enhance platelet hyperreactivity; Dectin-1-/- mice confirmed the Dectin-1 dependency of Galectin-3-potentiated thrombosis. Dectin-1 inhibitor (laminarin), Dectin-1-/- mice, platelet function studies, Ca2+ flux, ROS assays, in vivo thrombosis models European heart journal High 35165707
2023 Angiotensin II (Ang II) directly binds to Dectin-1 (a non-classical receptor), causing Dectin-1 homodimerization and activating the downstream Syk/NF-kappaB signaling pathway; mutagenesis identified residue R184 in the C-type lectin domain as critical for Ang II interaction; macrophage Dectin-1 mediates Ang II-induced cardiac inflammation through paracrine crosstalk with cardiomyocytes and fibroblasts. Molecular binding studies, site-directed mutagenesis (R184), Dectin-1-knockout mice, bone marrow transplantation chimeras, Syk/NF-kappaB signaling assays, macrophage co-culture with cardiomyocytes/fibroblasts Circulation research High 36786193
2023 Beta-amyloid (Abeta42) directly binds to Dectin-1 on microglia, causing Dectin-1 homodimerization and activating downstream Syk/NF-kappaB signaling to induce inflammatory factors and AD pathology; Dectin-1 knockout reduced Abeta42-induced microglial activation, inflammatory responses, and cognitive deficits. Direct binding studies (Abeta42-Dectin-1), Dectin-1 knockout mice, BV2 cell siRNA knockdown, Syk/NF-kappaB pathway analysis, behavioral testing International journal of biological sciences Medium 37416769
2019 Dectin-1 activation induces RIPK1-RIPK3-MLKL necroptosis in myeloid cells during Candida albicans infection; CARD9 was identified as the adaptor bridging the Dectin-1 signaling cascade to the RIPK1-RIPK3 complex; both MLKL-dependent and MLKL-independent (inflammatory) pathways downstream of RIPK1/RIPK3 are required for host defense. Genetic knockout models (RIPK1, RIPK3, MLKL, CARD9), Dectin-1 agonist stimulation, cell death assays in myeloid cells, in vivo C. albicans infection models Cell death and differentiation High 30944411
2015 Dectin-1 suppresses TLR4 signaling in hepatic inflammatory and stellate cells by mitigating TLR4 and CD14 expression via Dectin-1-dependent macrophage colony stimulating factor (M-CSF) expression; Dectin-1-/- mice show augmented cytokine production and reduced survival in LPS-mediated sepsis. Dectin-1-/- mice, LPS sepsis model, hepatic fibrosis and cancer models, TLR4/CD14 expression analysis, M-CSF measurement Cell reports Medium 26655905
2021 Dectin-1 limits experimental autoimmune encephalomyelitis (EAE) through a Card9-independent pathway in myeloid cells by inducing Oncostatin M (Osm) expression via the transcription factor NFAT; OsmR on astrocytes mediates the neuroprotective downstream effect; endogenous Dectin-1 ligands including galectin-9 in the CNS activate this pathway (not mycobacterial adjuvant). Dectin-1-/- and Card9-/- mice in EAE model, myeloid cell-specific analysis, NFAT inhibition, OsmR-/- astrocyte studies, galectin-9 ligand identification Immunity High 33581044
2019 Nanoscale proximity (<500 nm centroid-to-centroid distance) between Dectin-1 and TLR2 on phagosomes is required for synergistic innate immune signaling; receptor segregation beyond this threshold abolishes signaling synergy without changing overall membrane composition. Spatially patterned ligand particles, geometric manipulation technique, macrophage phagosome signaling assays, super-resolution microscopy Proceedings of the National Academy of Sciences of the United States of America High 31754039
2020 Dectin-1 stimulation by soluble beta-glucan drives RHOA-ROCK-myosin light chain (MLC) pathway-mediated mechanical force generation and areal contraction in Dectin-1-expressing cells; this force generation is Syk-independent but SFK-dependent; RHOA-ROCK-MLC signaling is required for Dectin-1-mediated phagocytosis of C. albicans. SYK and SFK inhibitors, RHOA activity assays, stress fiber staining, traction force measurements in HEK-293 transfectants and M1 macrophages, phagocytosis assays Journal of cell science Medium 31964711
2011 PPAR-gamma ligand troglitazone inhibits Dectin-1-mediated dendritic cell activation by interfering with CARD9 accumulation in the cytosol, and inhibiting downstream MAPK and NF-kappaB signaling, without affecting Dectin-1 expression or Syk phosphorylation. Pharmacological treatment (troglitazone), Western blotting for CARD9, MAPKs, NF-kappaB, surface molecule expression, cytokine ELISA in human monocyte-derived DCs Blood Medium 21296999
2017 Card9 is strictly required for Dectin-1-induced CTL cross-priming; Dectin-1-triggered Card9 signaling (but not inflammasome activation) drives expansion and activation of antigen-specific CTLs sufficient to protect against tumor challenge in mice. Card9-/- mice, in vitro cross-priming assays, in vivo vaccination and tumor challenge models, NK cell depletion experiments European journal of immunology Medium 28295265
2019 Core fucose on IgG antibodies is recognized by Dectin-1; biophysical experiments suggest Dectin-1 recognizes aromatic amino acids adjacent to the N-terminal asparagine at the glycosylation site as well as the core fucose, making Dectin-1 the first mammalian lectin recognizing characteristic N-glycans on antibodies. Biophysical binding experiments (SPR, NMR), glycan array, cell-based reporter assays Angewandte Chemie Medium 31625659
2023 Dectin-1 on colonic gamma-delta T cells mediates psychosocial stress-susceptible behaviors; stress-induced reduction of Lactobacillus species promotes increased differentiation of IL-17-producing colonic gamma-delta T cells (gamma-delta17 T cells) and their meningeal accumulation via Dectin-1 signaling. Dectin-1 genetic knockout, adoptive transfer, gut microbiota manipulation, flow cytometry of gamma-delta T cell subsets, behavioral testing Nature immunology Medium 36941398
2022 Human Dectin-1 deficiency (biallelic CLEC7A mutations) impairs macrophage TNF-alpha and IL-1beta production in response to beta-glucan; mouse macrophages require both Dectin-1 and CARD9 for IL-1beta and TNF-alpha production against Corynespora cassiicola, with these cytokines enhancing fungal killing in an interdependent manner. Patient PBMC functional assays, mouse macrophage genetic KO (Dectin-1-/-, CARD9-/-), mouse infection model, cytokine production and fungal killing assays The Journal of clinical investigation High 36377664
2022 Dectin-1 promotes FcgammaRIIb membrane conformations that allow productive IgG binding, acting as a co-inhibitory checkpoint for IVIg-dependent inhibition of osteoclastogenesis; IVIg-mediated inhibition of osteoclastogenesis is abrogated in Dectin-1-/- mice; Dectin-1 is required for FcgammaRIIb-dependent reprogramming of monocytes. Dectin-1-/- and FcgammaRIIb-/- mice, atomistic molecular dynamics simulations, super-resolution microscopy, human and mouse IgG subclass assays, osteoclastogenesis assays Immunity High 36948194
2024 Microglial Clec7a interacts with neuronal myeloid differentiation protein 2 (MD2) and regulates microglial phagocytosis of excitatory synapses after ischemic stroke; manipulating microglial Clec7a expression regulates synaptic phagocytosis and neurobehavioral outcomes. RNA sequencing of microglia, Clec7a gain/loss-of-function in ischemic stroke mouse model, co-immunoprecipitation (Clec7a-MD2 interaction), synaptic marker imaging, behavioral testing Advanced science Medium 39088351
2018 Neutrophil elastase (NE) cleaves Dectin-1 in an isoform-specific manner, with Dectin-1A more susceptible than Dectin-1B; Aspergillus fumigatus-derived fungal proteases similarly cleave Dectin-1 in an isoform-specific manner; Dectin-1 cleavage reduces phagocytosis of zymosan and fungal-induced cytokine production. Purified NE cleavage assays, CF patient BAL fluid, A. fumigatus protease filtrate, Dectin-1 KO cell controls, phagocytosis assays, cytokine production assays FASEB journal Medium 29401615
2017 Dectin-1 signaling inhibits osteoclastogenesis via IL-33-induced upregulation of MafB (an NFATc1 inhibitor) in osteoclast precursors; blocking the IL-33 receptor ST2 partially abrogates curdlan-induced NFATc1 inhibition, placing IL-33 downstream of Dectin-1 in this pathway. Curdlan (dectin-1 agonist) treatment, ST2 blocking, MafB and NFATc1 expression analysis, RANKL-induced osteoclast differentiation and bone resorption assays Oncotarget Medium 28881817
2021 Eosinophil extracellular DNA trap (EETosis) formation triggered by microfilariae is specifically dependent on Dectin-1 signaling; signaling via other C-type lectin receptors, antibody opsonization, or prior priming are not required; DNA released is mainly of mitochondrial origin. Dectin-1 genetic knockout, other CLR-deficient models, in vitro EETosis assays, scanning electron microscopy, confocal microscopy with specific markers, in vivo microfilaria injection Cell reports Medium 33440150
2024 Cell-intrinsic Dectin-1 activation in macrophages using depleted zymosan triggers generation of cell-intrinsic C5a, which acts on intracellular and cell surface C5aR1 to sustain mitochondrial ROS generation, upregulate TNF-alpha production, and enhance fungal killing; C5a synergizes with Dectin-1 to a greater extent than with TLRs. Human primary monocyte-derived macrophages, pharmacological inhibitors of C5aR1/C5aR2, Dectin-1 agonist (depleted zymosan), cytokine measurement, mitochondrial ROS assays, fungal killing assays Proceedings of the National Academy of Sciences of the United States of America Medium 38252818
2022 C/EBPbeta transcription factor directly binds the Clec7a promoter to upregulate Clec7a expression in neuropathic pain; C/EBPbeta knockdown suppresses Clec7a upregulation and downstream Syk/ERK/JNK phosphorylation, NLRP3 inflammasome activation, and pyroptosis; re-expression of Clec7a reverses these effects. Luciferase reporter assay, ChIP-qPCR, in vivo siRNA knockdown (CCI rat model), in vitro overexpression rescue, western blotting for Syk/ERK/JNK/NLRP3/Caspase-1/GSDMD Journal of translational medicine High 36503542

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Dectin-1: a signalling non-TLR pattern-recognition receptor. Nature reviews. Immunology 855 16341139
2002 Dectin-1 is a major beta-glucan receptor on macrophages. The Journal of experimental medicine 764 12163569
2019 Dectin-1 Contributes to Myocardial Ischemia/Reperfusion Injury by Regulating Macrophage Polarization and Neutrophil Infiltration. Circulation 233 30586706
2011 The role of Dectin-1 in the host defence against fungal infections. Current opinion in microbiology 230 21803640
2010 (1,3)-beta-glucans activate both dectin-1 and NLRP3 inflammasome in human macrophages. Journal of immunology (Baltimore, Md. : 1950) 224 20421639
2009 Pattern recognition: recent insights from Dectin-1. Current opinion in immunology 219 19223162
2004 Dectin-1 and its role in the recognition of beta-glucans by macrophages. Molecular immunology 204 14698225
2011 Dectin-1 and Dectin-2 in innate immunity against fungi. International immunology 179 21677049
2022 Dectin-1 Signaling Update: New Perspectives for Trained Immunity. Frontiers in immunology 154 35237264
2008 beta-Glucans and dectin-1. Annals of the New York Academy of Sciences 152 19076344
2007 Collaboration between the innate immune receptors dectin-1, TLRs, and Nods. Immunological reviews 140 17850483
2019 The macrophage tetraspan MS4A4A enhances dectin-1-dependent NK cell-mediated resistance to metastasis. Nature immunology 120 31263276
2012 Dectin-1 and DC-SIGN polymorphisms associated with invasive pulmonary Aspergillosis infection. PloS one 114 22384201
2007 The role of the beta-glucan receptor Dectin-1 in control of fungal infection. Journal of leukocyte biology 112 17475782
2020 Dectin-1/Syk signaling triggers neuroinflammation after ischemic stroke in mice. Journal of neuroinflammation 111 31926564
2012 Mechanisms of Fc receptor and dectin-1 activation for phagocytosis. Traffic (Copenhagen, Denmark) 99 22624959
2012 Dectin-1 isoforms contribute to distinct Th1/Th17 cell activation in mucosal candidiasis. Cellular & molecular immunology 92 22543832
2006 Expression of functionally different dectin-1 isoforms by murine macrophages. Journal of immunology (Baltimore, Md. : 1950) 90 16622020
2004 The role of Dectin-1 in antifungal immunity. Critical reviews in immunology 86 15482254
2023 Dectin-1 signaling on colonic γδ T cells promotes psychosocial stress responses. Nature immunology 80 36941398
2008 Fungal Recognition by TLR2 and Dectin-1. Handbook of experimental pharmacology 79 18071656
2015 Dectin-1 Regulates Hepatic Fibrosis and Hepatocarcinogenesis by Suppressing TLR4 Signaling Pathways. Cell reports 76 26655905
2002 Molecular and functional characterization of human Dectin-1. Experimental hematology 74 12423684
2021 The role of dectin-1 in health and disease. Immunobiology 73 33588306
2014 Dectin-1 pathway activates robust autophagy-dependent unconventional protein secretion in human macrophages. Journal of immunology (Baltimore, Md. : 1950) 73 24808366
2014 Dectin-1 induces M1 macrophages and prominent expansion of CD8+IL-17+ cells in pulmonary Paracoccidioidomycosis. The Journal of infectious diseases 70 24604821
2007 hDectin-1 is involved in uptake and cross-presentation of cellular antigens. Blood 70 17698636
2018 Dectin-1/2-induced autocrine PGE2 signaling licenses dendritic cells to prime Th2 responses. PLoS biology 69 29668708
2013 Dectin-1 activation controls maturation of β-1,3-glucan-containing phagosomes. The Journal of biological chemistry 68 23609446
2014 Innate immunity induced by fungal β-glucans via dectin-1 signaling pathway. International journal of medicinal mushrooms 67 24940900
2008 Susceptibility to Coccidioides species in C57BL/6 mice is associated with expression of a truncated splice variant of Dectin-1 (Clec7a). Genes and immunity 66 18418396
2021 Dectin-1 limits autoimmune neuroinflammation and promotes myeloid cell-astrocyte crosstalk via Card9-independent expression of Oncostatin M. Immunity 63 33581044
2018 Dectin-1-Syk-CARD9 Signaling Pathway in TB Immunity. Frontiers in immunology 63 29487599
2008 The pattern recognition receptor Dectin-1: from fungi to mycobacteria. Current drug targets 59 18288963
2016 Curdlan activates dendritic cells through dectin-1 and toll-like receptor 4 signaling. International immunopharmacology 58 27449326
2021 Emerging roles of Dectin-1 in noninfectious settings and in the CNS. Trends in immunology 53 34489167
2016 Particulate β-glucans synergistically activate TLR4 and Dectin-1 in human dendritic cells. Molecular nutrition & food research 51 27358258
2022 Galectin 3 enhances platelet aggregation and thrombosis via Dectin-1 activation: a translational study. European heart journal 48 35165707
2019 Dectin-1-Targeted Antifungal Liposomes Exhibit Enhanced Efficacy. mSphere 47 30760610
2014 Dectin-1 activation induces proliferation and migration of human keratinocytes enhancing wound re-epithelialization. Cellular immunology 47 24721111
2023 Cancer immunotherapy via synergistic coactivation of myeloid receptors CD40 and Dectin-1. Science immunology 45 37976347
2019 Dectin-1-induced RIPK1 and RIPK3 activation protects host against Candida albicans infection. Cell death and differentiation 45 30944411
2018 β‑glucan, a dectin‑1 ligand, promotes macrophage M1 polarization via NF‑κB/autophagy pathway. International journal of oncology 44 30431070
2016 Dectin-1 Controls TLR9 Trafficking to Phagosomes Containing β-1,3 Glucan. Journal of immunology (Baltimore, Md. : 1950) 44 26829985
2008 Dectin-1 and its role in antifungal immunity. Medical mycology 42 18608924
2001 Cloning of human DECTIN-1, a novel C-type lectin-like receptor gene expressed on dendritic cells. Immunogenetics 42 11491532
2017 Dectin-1 Activation Exacerbates Obesity and Insulin Resistance in the Absence of MyD88. Cell reports 41 28614714
2015 Recognition of Candida albicans by Dectin-1 induces mast cell activation. Immunobiology 41 26001731
2012 Macrophage dectin-1 expression is controlled by leukotriene B4 via a GM-CSF/PU.1 axis. Journal of immunology (Baltimore, Md. : 1950) 41 22696442
2023 β-amyloid binds to microglia Dectin-1 to induce inflammatory response in the pathogenesis of Alzheimer's disease. International journal of biological sciences 40 37416769
2015 Expression of dectin-1 and enhanced activation of NALP3 inflammasome are associated with resistance to paracoccidioidomycosis. Frontiers in microbiology 40 26388856
2015 Participation of dectin-1 receptor on NETs release against Paracoccidioides brasiliensis: Role on extracellular killing. Immunobiology 39 26416210
2023 Dectin-1 Acts as a Non-Classical Receptor of Ang II to Induce Cardiac Remodeling. Circulation research 38 36786193
2015 Dectin-1 activation unlocks IL12A expression and reveals the TH1 potency of neonatal dendritic cells. The Journal of allergy and clinical immunology 38 25865351
2024 Genetic variants of dectin-1 and their antifungal immunity impact in hematologic malignancies: A comprehensive systematic review. Current research in translational medicine 37 39038414
2022 Disruption of C/EBPβ-Clec7a axis exacerbates neuroinflammatory injury via NLRP3 inflammasome-mediated pyroptosis in experimental neuropathic pain. Journal of translational medicine 37 36503542
2021 Microfilariae Trigger Eosinophil Extracellular DNA Traps in a Dectin-1-Dependent Manner. Cell reports 36 33440150
2022 Regulating microglial miR-155 transcriptional phenotype alleviates Alzheimer's-induced retinal vasculopathy by limiting Clec7a/Galectin-3+ neurodegenerative microglia. Acta neuropathologica communications 35 36076283
2016 Triggering Dectin-1-Pathway Alone Is Not Sufficient to Induce Cytokine Production by Murine Macrophages. PloS one 35 26840954
2011 Protein kinase Cδ is a critical component of Dectin-1 signaling in primary human monocytes. Journal of leukocyte biology 35 21653233
2005 Dectin-1 escape by fungal dimorphism. Trends in immunology 34 15922664
2019 Geometrical reorganization of Dectin-1 and TLR2 on single phagosomes alters their synergistic immune signaling. Proceedings of the National Academy of Sciences of the United States of America 32 31754039
2024 The Dectin-1 and Dectin-2 clusters: C-type lectin receptors with fundamental roles in immunity. EMBO reports 31 39482490
2018 Wnt5a contributes to dectin-1 and LOX-1 induced host inflammatory response signature in Aspergillus fumigatus keratitis. Cellular signalling 31 30172652
2023 Levo-tetrahydropalmatine ameliorates neuropathic pain by inhibiting the activation of the Clec7a-MAPK/NF-κB-NLRP3 inflammasome axis. Phytomedicine : international journal of phytotherapy and phytopharmacology 30 37741158
2022 Human Dectin-1 deficiency impairs macrophage-mediated defense against phaeohyphomycosis. The Journal of clinical investigation 30 36377664
2018 Differential susceptibility of Dectin-1 isoforms to functional inactivation by neutrophil and fungal proteases. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 30 29401615
2021 Dectin-1-Mediated Production of Pro-Inflammatory Cytokines Induced by Yeast β-Glucans in Bovine Monocytes. Frontiers in immunology 29 34122455
2022 Deletion of both Dectin-1 and Dectin-2 affects the bacterial but not fungal gut microbiota and susceptibility to colitis in mice. Microbiome 27 35698210
2017 Dectin-1 intracellular domain determines species-specific ligand spectrum by modulating receptor sensitivity. The Journal of biological chemistry 26 28848046
2024 Clec7a Worsens Long-Term Outcomes after Ischemic Stroke by Aggravating Microglia-Mediated Synapse Elimination. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 25 39088351
2014 Induction and activation of human Th17 by targeting antigens to dendritic cells via dectin-1. Journal of immunology (Baltimore, Md. : 1950) 25 24835401
2011 Regulation of dectin-1-mediated dendritic cell activation by peroxisome proliferator-activated receptor-gamma ligand troglitazone. Blood 25 21296999
2019 The Core Fucose on an IgG Antibody is an Endogenous Ligand of Dectin-1. Angewandte Chemie (International ed. in English) 24 31625659
2023 Dectin-1 deficiency alleviates diabetic cardiomyopathy by attenuating macrophage-mediated inflammatory response. Biochimica et biophysica acta. Molecular basis of disease 23 37054997
2020 Distinct Roles for Dectin-1 and Dectin-2 in Skin Wound Healing and Neutrophilic Inflammatory Responses. The Journal of investigative dermatology 23 32511980
2019 Dependence on Dectin-1 Varies With Multiple Candida Species. Frontiers in microbiology 23 31447813
2017 MiR-146a negatively regulates dectin-1-induced inflammatory responses. Oncotarget 23 28454101
2019 IL13-Mediated Dectin-1 and Mannose Receptor Overexpression Promotes Macrophage Antitumor Activities through Recognition of Sialylated Tumor Cells. Cancer immunology research 22 30610060
2019 Dectin-1 genetic deficiency predicts chronic lung allograft dysfunction and death. JCI insight 22 31613800
2006 Human Dectin-1 isoform E is a cytoplasmic protein and interacts with RanBPM. Biochemical and biophysical research communications 22 16870151
2023 Immunoglobulin G-dependent inhibition of inflammatory bone remodeling requires pattern recognition receptor Dectin-1. Immunity 21 36948194
2017 Card9 controls Dectin-1-induced T-cell cytotoxicity and tumor growth in mice. European journal of immunology 21 28295265
2017 Dectin-1 signaling inhibits osteoclastogenesis via IL-33-induced inhibition of NFATc1. Oncotarget 21 28881817
2022 Preparation of a Nanobody Specific to Dectin 1 and Its Anti-inflammatory Effects on Fungal Keratitis. International journal of nanomedicine 20 35140463
2011 Dectin-1 and NOD2 mediate cathepsin activation in zymosan-induced arthritis in mice. Inflammation research : official journal of the European Histamine Research Society ... [et al.] 20 21424514
2020 RHOA-mediated mechanical force generation through Dectin-1. Journal of cell science 19 31964711
2017 Dectin-1 Compromises Innate Responses and Host Resistance against Neospora caninum Infection. Frontiers in immunology 19 28326085
2014 Expression of dectin-1 during fungus infection in human corneal epithelial cells. International journal of ophthalmology 19 24634860
2023 Dectin-1 multimerization and signaling depends on fungal β-glucan structure and exposure. Biophysical journal 18 37515324
2021 Dectin-1 Controls TSLP-Induced Th2 Response by Regulating STAT3, STAT6, and p50-RelB Activities in Dendritic Cells. Frontiers in immunology 18 34305908
2024 Cell-intrinsic C5a synergizes with Dectin-1 in macrophages to mediate fungal killing. Proceedings of the National Academy of Sciences of the United States of America 17 38252818
2024 Dectin-1 aggravates neutrophil inflammation through caspase-11/4-mediated macrophage pyroptosis in asthma. Respiratory research 17 38459541
2023 Macrophage Dectin-1 mediates Ang II renal injury through neutrophil migration and TGF-β1 secretion. Cellular and molecular life sciences : CMLS 17 37340199
2021 Role and mechanism of the Dectin-1-mediated Syk/NF-κB signaling pathway in Talaromyces marneffei infection. Experimental and therapeutic medicine 16 34938366
2023 Identification of Clec7a as the therapeutic target of rTMS in alleviating Parkinson's disease: targeting neuroinflammation. Biochimica et biophysica acta. Molecular basis of disease 15 37495085
2019 Exopolysaccharides from Cyanobacterium aponinum induce a regulatory dendritic cell phenotype and inhibit SYK and CLEC7A expression in dendritic cells, T cells and keratinocytes. International immunopharmacology 15 30772700
2023 Dectin-1-Independent Macrophage Phagocytosis of Mycobacterium abscessus. International journal of molecular sciences 14 37446240
2021 Paracoccidioides brasiliensis activates mesenchymal stem cells through TLR2, TLR4, and Dectin-1. Medical mycology 14 32459842
2018 A Comprehensive in Silico Analysis of Regulatory SNPs of Human CLEC7A Gene and Its Validation as Genotypic and Phenotypic Disease Marker in Recurrent Vulvovaginal Infections. Frontiers in cellular and infection microbiology 14 29616193

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