Affinage

CLEC7A

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

Length
247 aa
Mass
27.6 kDa
Annotated
2026-04-28
100 papers in source corpus 35 papers cited in narrative 35 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CLEC7A (Dectin-1) is a type II transmembrane C-type lectin receptor on myeloid cells that functions as the principal pattern recognition receptor for β-1,3/1,6-glucans and orchestrates antifungal immunity, phagolysosomal maturation, and inflammatory signaling. Its extracellular CTLD binds β-glucans cooperatively, forming ligand-induced tetramers; particulate ligands cluster Dectin-1 into a phagocytic synapse that excludes the phosphatases CD45 and CD148, enabling hemITAM phosphorylation by Src kinases, Syk recruitment, PLCγ2-dependent Ca²⁺ flux, CARD9–Bcl10–Malt1-mediated NF-κB activation, NLRP3 inflammasome engagement, and ROS production, while Syk further drives phagosomal maturation and TLR9 trafficking (PMID:12163569, PMID:21525931, PMID:19136564, PMID:23609446, PMID:29897456, PMID:26829985). Signaling is amplified by co-receptors MS4A4A and CD82 in lipid rafts and requires nanoscale proximity with TLR2 for synergy, while it is attenuated by receptor internalization and SPPL2a/b-mediated intramembrane proteolysis (PMID:31263276, PMID:31010852, PMID:31754039, PMID:19130473, PMID:35388002). Beyond β-glucans, Dectin-1 recognizes endogenous ligands including galectin-9 (driving tolerogenic macrophage programming in pancreatic cancer), galectin-3 (activating platelets), angiotensin II, and β-amyloid, each engaging the Syk/NF-κB cascade in tissue-specific contexts; biallelic loss-of-function CLEC7A mutations cause susceptibility to invasive fungal infections including mucocutaneous candidiasis and phaeohyphomycosis (PMID:28394331, PMID:35165707, PMID:36786193, PMID:37416769, PMID:19864674, PMID:36377664).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2000 Medium

    Identification of Dectin-1 as a novel type II transmembrane C-type lectin on dendritic cells established the gene product and suggested a role in T cell co-stimulation, but its physiological ligand was unknown.

    Evidence Subtractive cDNA cloning from a dendritic cell library, recombinant protein binding and T cell proliferation assays

    PMID:10779524

    Open questions at the time
    • Endogenous ligand unidentified
    • Expression pattern on other leukocytes unknown
    • Signaling pathway not characterized
  2. 2002 High

    Demonstration that Dectin-1 is the dominant β-glucan receptor on macrophages resolved what receptor mediates non-opsonic zymosan recognition and placed Dectin-1 at the center of fungal pattern recognition.

    Evidence Blocking mAb (2A11) nearly abolished β-glucan binding on primary macrophages; CD11b KO and carbohydrate inhibitor controls

    PMID:12163569

    Open questions at the time
    • Downstream signaling pathway uncharacterized
    • In vivo relevance of Dectin-1 for antifungal defense not yet tested
  3. 2005 High

    Linking Dectin-1 to Syk kinase activation and ROS production defined the core signaling axis downstream of β-glucan engagement and separated signaling from phagocytosis.

    Evidence Syk inhibitors and dominant-negative Syk in macrophages; ROS blocked but phagocytosis preserved

    PMID:15956283

    Open questions at the time
    • Adaptor complexes downstream of Syk not yet identified
    • PLCγ isoform involvement unknown
  4. 2006 High

    Genetic knockout in mice proved Dectin-1 is essential for protective antifungal immunity in vivo, and cooperative signaling with TLR2 (but not TLR4) was established for mycobacterial responses, broadening Dectin-1's pathogen repertoire beyond fungi.

    Evidence Dectin-1 KO mice with increased C. albicans burden and mortality; multiple KO macrophages (TLR2/4/MR/CR3/MyD88/Dectin-1) with mycobacterial cytokine assays

    PMID:16825490 PMID:17159984

    Open questions at the time
    • Mechanism of TLR2–Dectin-1 cooperation at receptor level unknown
    • Splice isoform functional significance in vivo unclear
  5. 2007 High

    Crystal structure of the Dectin-1 CTLD with a trapped β-glucan fragment provided the first atomic-level view of ligand recognition and revealed higher-order complex formation.

    Evidence X-ray crystallography at 2.8 Å resolution with in vitro biophysical validation

    PMID:17473009

    Open questions at the time
    • Full-length receptor structure unavailable
    • Cooperative oligomerization mechanism not yet defined
  6. 2009 High

    Three advances resolved the downstream signaling cascade and its regulation: PLCγ2 was identified as the critical phospholipase linking Syk to Ca²⁺ flux, MAPK, NF-κB (via CARD9–Bcl10–Malt1), and cytokine output; receptor internalization was shown to terminate signaling; and the human Y238X truncation mutation demonstrated that Dectin-1 loss-of-function causes susceptibility to mucocutaneous candidiasis.

    Evidence PLCγ2 KO dendritic cells with multiple pathway readouts; actin/dynamin inhibitors and non-phagocytosable particles prolonging signaling; patient PBMC functional assays with Y238X mutation

    PMID:19130473 PMID:19136564 PMID:19864674

    Open questions at the time
    • Whether internalization-dependent attenuation involves specific degradation machinery unknown
    • Relationship between hemITAM phosphorylation and phosphatase exclusion not yet tested
  7. 2011 High

    The phagocytic synapse model explained why only particulate β-glucans activate Dectin-1: clustering excludes CD45/CD148 phosphatases, enabling hemITAM phosphorylation — a mechanism analogous to the immunological synapse.

    Evidence Live-cell imaging with phosphatase exclusion microscopy; soluble vs. particulate ligand comparisons with Syk activation and ROS readouts

    PMID:21525931

    Open questions at the time
    • Identity of Src family kinase(s) mediating initial phosphorylation not pinpointed
    • Structural basis for phosphatase exclusion by Dectin-1 clusters unknown
  8. 2013 High

    Dectin-1 was established as a master regulator of phagolysosomal maturation: Syk-dependent signaling controls Rab5B-to-LAMP-1 transition and phagosomal acidification, linking receptor signaling to intracellular pathogen destruction.

    Evidence GFP-Dectin-1 live imaging, signaling-incompetent mutants, Src/Syk inhibitors, phagosomal marker and pH measurements

    PMID:23609446

    Open questions at the time
    • Specific GEFs/GAPs linking Syk to Rab switching not identified
    • Whether other CLRs share this maturation-control mechanism unknown
  9. 2016 High

    Dectin-1/Syk signaling was found to control TLR9 trafficking to fungal phagosomes, establishing a mechanism by which Dectin-1 integrates innate sensing of β-glucan with nucleic acid recognition.

    Evidence Dectin-1-deficient cells and Syk inhibitors; TLR9 localization imaging with phagosomal acidification inhibitors

    PMID:26829985

    Open questions at the time
    • Motor or trafficking machinery moving TLR9 to phagosomes not identified
    • Whether this mechanism extends to other endosomal TLRs unknown
  10. 2017 High

    Galectin-9 was identified as the first endogenous Dectin-1 ligand with pathological significance: ligation drives tolerogenic macrophage programming and immune suppression in pancreatic ductal adenocarcinoma.

    Evidence Binding assays, Clec7a KO mice, bone marrow chimeras, and tumor progression models

    PMID:28394331

    Open questions at the time
    • Binding site on Dectin-1 for galectin-9 not mapped
    • Whether galectin-9–Dectin-1 engages identical downstream pathway as β-glucan not fully resolved
  11. 2018 High

    Multiple advances refined the biophysical and cellular mechanisms: cooperative CTLD tetramerization upon laminarin binding was characterized (Hill coefficient ~3); N-glycosylation was shown to control isoform A surface expression; and Dectin-1/Syk was linked to NLRP3 inflammasome activation during mycobacterial infection.

    Evidence SEC-MALS, mutagenesis, and tryptophan fluorescence for oligomerization; glycosylation inhibitors with isoform-specific cell lines; NLRP3/ASC knockdown with caspase-1 assays in human macrophages

    PMID:21876553 PMID:28303575 PMID:29897456

    Open questions at the time
    • Full-length oligomeric structure on membrane not resolved
    • Relationship between tetramerization and phagocytic synapse formation not tested
  12. 2019 High

    Co-receptor requirements and signaling crosstalk were defined: MS4A4A and CD82 promote Dectin-1 clustering and Src/Syk activation in lipid rafts; TLR2 synergy requires nanoscale proximity (<500 nm); galectin-3 activates platelet Dectin-1; and CARD9 bridges RIPK1–RIPK3 to drive Dectin-1-dependent necroptosis.

    Evidence Ms4a4a and CD82 KO macrophages with Co-IP and functional assays; spatially patterned ligand particles for TLR2 proximity; Dectin-1 KO platelet assays and thrombosis models; RIPK1/RIPK3/MLKL KO cells with C. albicans infection

    PMID:30944411 PMID:31010852 PMID:31263276 PMID:31754039 PMID:35165707

    Open questions at the time
    • Stoichiometry of MS4A4A and CD82 within the Dectin-1 signaling complex unknown
    • How CARD9 physically bridges RIPK1–RIPK3 not structurally resolved
  13. 2022 High

    SPPL2a/b-mediated intramembrane proteolysis of Dectin-1 after internalization was identified as a second layer of signal attenuation; biallelic CLEC7A mutations were linked to severe phaeohyphomycosis in humans, expanding the spectrum of Dectin-1 deficiency syndromes.

    Evidence SPPL2a/b KO immune cells with cleavage product characterization and enhanced ROS/cytokines; patient genetics with PBMC functional assays and Dectin-1/CARD9 KO mouse validation

    PMID:35388002 PMID:36377664

    Open questions at the time
    • Fate and signaling competence of the SPPL2-generated intracellular fragment not fully characterized
    • Full clinical spectrum of human Dectin-1 deficiency not delineated
  14. 2023 High

    Dectin-1's ligand repertoire was substantially broadened: angiotensin II (binding at R184) and β-amyloid were shown to directly engage the CTLD, driving homodimerization and Syk/NF-κB-dependent inflammation in cardiac and neuroinflammatory contexts, respectively.

    Evidence Direct binding assays with mutagenesis (R184) and Dectin-1 KO in cardiac remodeling models; binding and KO studies in Alzheimer's disease mouse models

    PMID:36786193 PMID:37416769

    Open questions at the time
    • Whether angiotensin II and β-amyloid compete with β-glucan for binding unknown
    • Structural basis for CTLD recognition of non-carbohydrate ligands not resolved
  15. 2023 Medium

    Dectin-1 function was extended beyond classical myeloid cells: expression on colonic γδ T cells promotes IL-17-producing γδ17 differentiation and stress-susceptible behavior via gut–brain axis signaling, and Dectin-1 modulates FcγRIIb conformation to regulate IgG-dependent osteoclastogenesis inhibition.

    Evidence Dectin-1 KO with colonic T cell transfer and behavioral assays; Dectin-1/FcγRIIb KO with super-resolution microscopy, MD simulations, and osteoclastogenesis assays

    PMID:36941398 PMID:36948194

    Open questions at the time
    • Ligand activating Dectin-1 on γδ T cells not identified
    • How Dectin-1 alters FcγRIIb membrane conformation at molecular level not experimentally resolved beyond simulation

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis for Dectin-1 recognition of its diverse non-carbohydrate ligands, the full-length receptor architecture in membranes (including oligomeric state), the signaling competence of SPPL2-generated fragments, and how tissue-specific co-receptor assemblies determine divergent downstream outcomes.
  • No full-length Dectin-1 structure in membrane context
  • Signaling competence of SPPL2a/b cleavage products unclear
  • How the same Syk cascade yields tolerogenic vs. inflammatory outputs in different tissues not mechanistically resolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 5 GO:0140299 molecular sensor activity 3 GO:0098772 molecular function regulator activity 1
Localization
GO:0005886 plasma membrane 5 GO:0005764 lysosome 3 GO:0031410 cytoplasmic vesicle 3
Pathway
R-HSA-168256 Immune System 10 R-HSA-162582 Signal Transduction 7 R-HSA-1643685 Disease 3 R-HSA-5357801 Programmed Cell Death 1
Partners
CARD9CD82LGALS3LGALS9MS4A4APLCG2SYKTLR2

Evidence

Reading pass · 35 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 Dectin-1 (CLEC7A) was identified as a type II transmembrane protein with a C-terminal C-type lectin-like domain (carbohydrate recognition domain); recombinant extracellular domain bound T cell surfaces and promoted T cell proliferation in the presence of anti-CD3, suggesting a co-stimulatory function. Subtractive cDNA cloning, recombinant protein binding assays, T cell proliferation assay The Journal of biological chemistry Medium 10779524
2002 Dectin-1 is the predominant beta-glucan receptor on primary macrophages responsible for non-opsonic recognition of zymosan; anti-Dectin-1 mAb (2A11) almost completely blocked beta-glucan-dependent zymosan binding, establishing Dectin-1 as the leukocyte beta-glucan receptor. Blocking monoclonal antibody, genetic CD11b knockout controls, carbohydrate inhibitors, flow cytometry The Journal of experimental medicine High 12163569
2005 Dectin-1 activates spleen tyrosine kinase (Syk) in macrophages upon beta-glucan engagement, and this Syk activation is required for reactive oxygen species (ROS) production but not for phagocytosis; Syk activation is restricted to a dynamic subset of macrophages. Syk inhibitor studies, dominant-negative Syk, ROS assays, phagocytosis assays in macrophages Blood High 15956283
2006 Dectin-1 deficiency in mice renders them susceptible to Candida albicans infection; Dectin-1-deficient leukocytes have impaired responses to fungi even in the presence of opsonins, with reduced inflammatory cell recruitment and increased fungal burden in vivo, establishing Dectin-1 as essential for protective antifungal immunity. Dectin-1 knockout mouse model, in vivo fungal infection, leukocyte functional assays Nature immunology High 17159984
2006 Mice express at least two splice isoforms of Dectin-1 (Dectin-1A with stalk, Dectin-1B without stalk) that are functionally distinct: both bind and phagocytose zymosan, but Dectin-1B binding is more temperature-sensitive and the isoforms differ in their ability to induce TNF-alpha production; equivalent human isoforms share these properties. RT-PCR isoform identification, stable expression in NIH-3T3 and RAW264.7 cells, phagocytosis and cytokine assays Journal of immunology Medium 16622020
2006 Dectin-1 functions together with TLR2 (but not TLR4, MR, or CR3) to mediate macrophage TNF-alpha production in response to mycobacterial infections; dectin-1-deficient macrophages infected with M. smegmatis, M. bovis BCG, M. phlei, M. avium 2151-rough, and M. tuberculosis H37Ra had significantly reduced TNF-alpha, IL-6, RANTES, and G-CSF production. Bone marrow-derived macrophages from TLR2, TLR4, MR, CR3, MyD88, and Dectin-1 knockout mice; cytokine ELISA Blood High 16825490
2007 Crystal structure of murine Dectin-1 extracellular C-type lectin-like domain (CTLD) was solved; a short beta-glucan was trapped in the crystal lattice at 2.8 Å resolution; in vitro biophysical studies showed higher-order complex formation between Dectin-1 and beta-glucans. X-ray crystallography, in vitro biophysical characterization Protein science High 17473009
2008 Dectin-1 and DC-SIGN are co-immunoprecipitated from human monocyte-derived dendritic cell lysates and confirmed to interact when Myc-Dectin-1 and DC-SIGN constructs are co-expressed in HEK293 cells; costimulation of both receptors synergistically triggers the arachidonic acid cascade, including cyclooxygenase-2 induction and leukotriene C4 biosynthesis. Reciprocal co-immunoprecipitation, HEK293 co-expression, eicosanoid assays, Syk inhibitors Journal of immunology Medium 18390758
2009 PLCgamma2 (not PLCgamma1) is the critical downstream signaling enzyme for Dectin-1 in dendritic cells: zymosan or curdlan stimulation of Dectin-1 induces phosphorylation of both PLCgamma1 and PLCgamma2, but PLCgamma2-deficient DCs have severely impaired Ca2+ flux, cytokine production (IL-2, IL-6, IL-10, IL-12, IL-23, TNF-alpha), ERK and JNK MAPK activation, AP-1 and NFAT activation, and NF-kappaB activation through defective Card9-Bcl10-Malt1 complex assembly. PLCgamma2 knockout DCs, Ca2+ flux assays, ELISA, immunoblotting, reporter assays The Journal of biological chemistry High 19136564
2009 Internalization of Dectin-1 after ligand binding terminates pro-inflammatory signaling: blocking phagocytosis (via actin/dynamin inhibitors, large non-phagocytosable particles, or poorly phagocytic cells) results in enhanced and sustained downstream signaling and higher cytokine production, demonstrating that internalization is the first step in attenuation of Dectin-1-mediated inflammatory responses. Actin polymerization inhibitors, dynamin inhibitors, large non-phagocytosable beta-glucan particles, poorly phagocytic cell lines, cytokine and signaling assays European journal of immunology High 19130473
2009 Human CLEC7A Y238X truncation mutation results in a form of Dectin-1 that is poorly expressed, does not mediate beta-glucan binding, and leads to defective cytokine production (IL-17, TNF, IL-6) in response to beta-glucan or C. albicans; fungal phagocytosis and killing were normal, dissecting the receptor's cytokine-signaling function from its phagocytic function. Patient PBMC functional assays, receptor binding studies, cytokine ELISAs, phagocytosis/killing assays The New England journal of medicine High 19864674
2011 Dectin-1 signaling is selectively activated by particulate (not soluble) beta-glucans through formation of a 'phagocytic synapse': particulate beta-glucans cluster Dectin-1 into synapse-like structures from which regulatory tyrosine phosphatases CD45 and CD148 are excluded, enabling Syk activation and downstream antimicrobial responses (phagocytosis and ROS production). Live cell imaging, ROS assays, phosphatase exclusion microscopy, soluble vs. particulate ligand comparisons Nature High 21525931
2011 Fungal recognition via beta-glucan on C. albicans and A. fumigatus (and bioactive particulate beta-glucan) triggers enhanced shedding of the mannose receptor (MR) in a Dectin-1-dependent manner; the canonical Syk-mediated pathway is mainly responsible, with Raf-1 partially involved, and metalloprotease activity required. Dectin-1 blocking antibodies, specific pathway inhibitors (Syk, Raf-1), metalloprotease inhibitors, sMR quantification The Journal of biological chemistry Medium 21205820
2013 Dectin-1 translocates to the fungal phagosome after beta-1,3-glucan recognition, undergoes tyrosine phosphorylation by Src kinases with subsequent Syk activation; Syk activation (but not intraphagosomal pH) controls phagosomal maturation: signaling-incompetent Dectin-1 mutants lead to prolonged Dectin-1 phagosomal retention, retention of Rab5B, failure to acquire LAMP-1, and inability to acidify, establishing Dectin-1 as a master regulator of phagolysosomal maturation. GFP-Dectin-1 live imaging, Src/Syk inhibitors, signaling-incompetent Dectin-1 mutants, phagosomal marker assays (LAMP-1, Rab5B, pH) The Journal of biological chemistry High 23609446
2016 Dectin-1-mediated Syk activation is required for TLR9 trafficking to beta-1,3-glucan-, A. fumigatus-, and C. albicans-containing phagosomes; Dectin-1 controls TLR9 redistribution in a Syk-dependent and phagosomal acidification-dependent manner, and regulates TLR9-dependent gene expression. Dectin-1 and Syk inhibitors, TLR9 localization imaging, Dectin-1-deficient cells, phagosomal acidification inhibitors Journal of immunology High 26829985
2017 Dectin-1 can ligate galectin-9 in mouse and human pancreatic ductal adenocarcinoma; Dectin-1 ligation by galectin-9 results in tolerogenic macrophage programming and adaptive immune suppression; deletion of Clec7a or blockade of downstream signaling is protective against PDA progression. Co-ligation/binding assays, Clec7a knockout mice, bone marrow chimeras, tumor progression models Nature medicine High 28394331
2017 The intracellular domain (not the ligand-binding domain) of Dectin-1 determines species-specific ligand sensitivity: two amino acids (Glu2/Pro5 in human vs. Lys2/Ser5 in mouse) in the cytoplasmic tail are sufficient to confer sensitivity to low-valency beta-glucan ligands (laminarin) in human but not mouse Dectin-1. Reciprocal mutagenesis, reporter cell assays, dendritic cell cytokine assays The Journal of biological chemistry High 28848046
2018 Beta-glucan-induced cooperative oligomerization of the Dectin-1 C-type lectin-like domain (CTLD): laminarin binding induces a tetramer (4 CTLD + 4 laminarin); residues W221, H223, and Y228 form a hydrophobic groove essential for beta-glucan binding and oligomerization, while residues Y141, R145, and E243 mediate protein-protein interactions; wild-type CTLD binds laminarin cooperatively (Hill coefficient ~3). Size exclusion chromatography, multi-angle light scattering, site-directed mutagenesis, intrinsic tryptophan fluorescence Glycobiology High 29897456
2018 MS4A4A interacts and co-localizes with Dectin-1 in lipid rafts on macrophages; Ms4a4a-deficient macrophages show defective Dectin-1 downstream signaling and defective production of effector molecules in response to Dectin-1 ligands; Ms4a4a deficiency impairs Dectin-1-mediated NK cell-mediated metastasis control. Co-immunoprecipitation, lipid raft fractionation, Ms4a4a KO macrophages, in vitro signaling assays, tumor metastasis models Nature immunology High 31263276
2019 Tetraspanin CD82 associates with Dectin-1 on plasma membranes and phagosomes; CD82 deletion results in diminished Dectin-1 clustering in the phagocytic cup, reduced Src and Syk phosphorylation, impaired ROS production, reduced cytokine production (TNF-alpha, IL-1beta), increased C. albicans viability in macrophages, and greater susceptibility in vivo. Co-immunoprecipitation, confocal microscopy, CD82 KO mice, Syk/Src phosphorylation assays, ROS assays, fungal killing assays Journal of immunology High 31010852
2019 Dectin-1 signaling requires nanoscale proximity (<500 nm centroid-to-centroid) with TLR2 for synergistic immune responses: when Dectin-1 and TLR2 are segregated to opposite sides of a single phagosome, their signaling synergy is abolished; co-localization is not required but nanoscale proximity is. Geometric manipulation of receptor positioning using spatially patterned ligand particles, single-phagosome microscopy, cytokine measurement Proceedings of the National Academy of Sciences High 31754039
2019 Galectin-3 binds to and activates Dectin-1 on platelets (a previously unrecognized Dectin-1 expression site), causing Syk phosphorylation, Ca2+ influx, PKC activation, and ROS production, thereby enhancing platelet hyperreactivity and thrombosis; Dectin-1 inhibition (laminarin) and Dectin-1 KO mice confirm this pathway. Dectin-1 inhibitor (laminarin), Dectin-1 KO mice, platelet aggregation assays, Ca2+ flux, ROS production, in vivo thrombosis models European heart journal High 35165707
2019 Candida albicans and Dectin-1 activation strongly induce myeloid cell necroptosis via RIPK1-RIPK3-MLKL cascade; CARD9, a key adaptor in Dectin-1 signaling, bridges the RIPK1-RIPK3 complex; both MLKL-dependent necroptosis and MLKL-independent inflammatory responses through RIPK1/RIPK3 contribute to host defense against C. albicans. RIPK1, RIPK3, MLKL knockout cells/mice, CARD9 genetic studies, in vitro and in vivo C. albicans infection models Cell death and differentiation High 30944411
2019 Dectin-1 core fucose recognition: Dectin-1 recognizes the core fucose on IgG N-glycans; biophysical experiments showed Dectin-1 also recognizes aromatic amino acids adjacent to the glycosylation site asparagine, identifying Dectin-1 as the first mammalian lectin for heterovalent specific recognition of core-fucosylated N-glycans on antibodies. Biophysical binding assays (NMR, SPR), glycan array, mutagenesis of IgG N-glycan structure Angewandte Chemie Medium 31625659
2022 Dectin-1a isoform undergoes intramembrane proteolysis by Signal Peptide Peptidase-like (SPPL) 2a and SPPL2b after ligand-induced internalization: pathogen recognition generates a stable receptor fragment lacking the ligand-binding domain that persists in phagosomal membranes and contributes to signal transduction; cells lacking SPPL2b show increased antifungal ROS production, killing, and cytokine responses. SPPL2a/2b knockout immune cells, biochemical characterization of Dectin-1 cleavage products, ROS and cytokine assays, fungal killing assays Nature communications High 35388002
2022 Human Dectin-1 deficiency (biallelic CLEC7A mutations) is identified in patients with severe phaeohyphomycosis; patient PBMCs fail to produce TNF-alpha and IL-1beta in response to beta-glucan/C. cassiicola; mouse macrophages require Dectin-1 and CARD9 for IL-1beta and TNF-alpha production, which mediate fungal killing in an interdependent manner. Patient genetic analysis, PBMC functional assays, Dectin-1 and CARD9 KO mouse models, in vitro killing assays The Journal of clinical investigation High 36377664
2023 Angiotensin II (Ang II) directly binds to macrophage Dectin-1 (residue R184 in the C-type lectin domain identified by mutagenesis), causing Dectin-1 homodimerization and activating downstream Syk/NF-kappaB signaling to induce inflammatory and chemoattractant factors, leading to cardiac remodeling; Dectin-1 KO and bone marrow chimera studies confirm bone marrow-derived cell Dectin-1 mediates Ang II-induced cardiac inflammation. Dectin-1 KO mice, bone marrow transplantation chimeras, direct binding assays, mutagenesis (R184), co-IP, Syk/NF-kappaB pathway analysis Circulation research High 36786193
2023 Beta-amyloid (Abeta42) directly binds to microglial Dectin-1, causing Dectin-1 homodimerization and activating downstream Syk/NF-kappaB signaling to induce inflammatory factors; Dectin-1 KO reduces Abeta42-induced microglial activation, inflammatory responses, and synaptic/cognitive deficits in an AD mouse model. Direct binding assays, Dectin-1 KO mice and BV2 cells, Syk/NF-kappaB pathway analysis, behavioral tests International journal of biological sciences Medium 37416769
2023 Dectin-1 and CD40 synergistically activate myeloid cells to eradicate tumors in pancreatic cancer models; antitumor activity requires cDC1s and T cells; CD40 drives T cell-mediated IFN-gamma signaling that converges with Dectin-1 activation to program distinct macrophage subsets. Mouse pancreatic cancer models, Dectin-1 KO, cDC1 depletion, beta-glucan systemic therapy, CD40 agonist antibody, flow cytometry Science immunology Medium 37976347
2023 Dectin-1 signaling in colonic gamma-delta T cells mediates stress-susceptible behaviors: dectin-1 expressed by gamma-delta T cells promotes their differentiation into IL-17-producing gamma-delta17 T cells and meningeal accumulation in response to psychosocial stress; this is dependent on altered Lactobacillus composition. Dectin-1 KO mice, colonic T cell isolation and transfer, meningeal immune cell quantification, behavioral tests, microbiome analysis Nature immunology Medium 36941398
2023 Dectin-1 promotes FcgammaRIIb membrane conformations allowing productive IgG binding (shown by molecular dynamics simulations and super-resolution microscopy), and IVIg-dependent inhibition of osteoclastogenesis requires both Dectin-1 and FcgammaRIIb; Dectin-1 acts as a co-inhibitory checkpoint for IgG-dependent inhibition of osteoclastogenesis. Dectin-1 KO mice, FcgammaRIIb KO mice, super-resolution microscopy, molecular dynamics simulations, in vitro osteoclastogenesis assays Immunity Medium 36948194
2024 Microglial Clec7a interacts with neuronal MD2 and mediates phagocytosis of excitatory synapses after ischemic stroke; manipulating microglial Clec7a expression regulates microglial synaptic phagocytosis, preventing synaptic loss and improving neurobehavioral outcomes. RNA sequencing of microglia, IS mouse model, Clec7a expression manipulation (gain/loss of function), co-interaction studies (Clec7a-MD2), behavioral assessment, synaptic quantification Advanced science Medium 39088351
2018 N-glycosylation of Dectin-1 isoform A is essential for its cell surface expression; non-glycosylated isoform B is retained intracellularly; inhibition of glycosylation abrogates cell surface expression of isoform A, resulting in reduced signaling quality and differential cytokine secretion. Flow cytometry, confocal microscopy, glycosylation inhibitors, stable isoform-expressing cell lines, cytokine bead array European journal of immunology Medium 28303575
2018 Dectin-1 triggers NLRP3 inflammasome activation via Dectin-1/Syk-dependent signaling in macrophages infected with Mycobacterium abscessus; Dectin-1-dependent Syk signaling (not MyD88) leads to caspase-1 activation and IL-1beta secretion through NLRP3/ASC inflammasome, and this requires p62/SQSTM1. Dectin-1 and TLR2 blocking antibodies, Syk inhibitors, NLRP3/ASC overexpression/knockdown, caspase-1 activation assays, potassium efflux studies in human macrophages Immunology and cell biology Medium 21876553
2018 Invertebrate tropomyosin is identified as an immunobiologically relevant endogenous Dectin-1 ligand on respiratory epithelial cells; Dectin-1 signaling through tropomyosin suppresses IL-33 secretion and dampens type 2 immunity; this pathway is impaired in asthmatic epithelial cells. Dectin-1 KO mice, ligand binding assays, IL-33 secretion assays, innate lymphoid cell recruitment assays, human epithelial cell experiments Science immunology Medium 29475849

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Dectin-1 is required for beta-glucan recognition and control of fungal infection. Nature immunology 925 17159984
2006 Dectin-1: a signalling non-TLR pattern-recognition receptor. Nature reviews. Immunology 848 16341139
2002 Dectin-1 is a major beta-glucan receptor on macrophages. The Journal of experimental medicine 758 12163569
2011 Activation of the innate immune receptor Dectin-1 upon formation of a 'phagocytic synapse'. Nature 650 21525931
2009 Human dectin-1 deficiency and mucocutaneous fungal infections. The New England journal of medicine 577 19864674
2005 Dectin-1 activates Syk tyrosine kinase in a dynamic subset of macrophages for reactive oxygen production. Blood 394 15956283
2005 The beta-glucan receptor dectin-1 recognizes specific morphologies of Aspergillus fumigatus. PLoS pathogens 394 16344862
2000 Identification of a novel, dendritic cell-associated molecule, dectin-1, by subtractive cDNA cloning. The Journal of biological chemistry 351 10779524
2006 The beta-glucan receptor dectin-1 functions together with TLR2 to mediate macrophage activation by mycobacteria. Blood 308 16825490
2017 Dectin 1 activation on macrophages by galectin 9 promotes pancreatic carcinoma and peritumoral immune tolerance. Nature medicine 306 28394331
2011 The role of Dectin-1 in the host defence against fungal infections. Current opinion in microbiology 228 21803640
2019 Dectin-1 Contributes to Myocardial Ischemia/Reperfusion Injury by Regulating Macrophage Polarization and Neutrophil Infiltration. Circulation 224 30586706
2008 DC activated via dectin-1 convert Treg into IL-17 producers. European journal of immunology 219 19039774
2009 Pattern recognition: recent insights from Dectin-1. Current opinion in immunology 217 19223162
2010 Distinct roles for Dectin-1 and TLR4 in the pathogenesis of Aspergillus fumigatus keratitis. PLoS pathogens 152 20617171
2008 beta-Glucans and dectin-1. Annals of the New York Academy of Sciences 151 19076344
2022 Dectin-1 Signaling Update: New Perspectives for Trained Immunity. Frontiers in immunology 144 35237264
2007 Collaboration between the innate immune receptors dectin-1, TLRs, and Nods. Immunological reviews 140 17850483
2009 Phospholipase Cgamma2 is critical for Dectin-1-mediated Ca2+ flux and cytokine production in dendritic cells. The Journal of biological chemistry 133 19136564
2015 Neuroinflammation triggered by β-glucan/dectin-1 signaling enables CNS axon regeneration. Proceedings of the National Academy of Sciences of the United States of America 127 25675510
2007 Structure of the fungal beta-glucan-binding immune receptor dectin-1: implications for function. Protein science : a publication of the Protein Society 122 17473009
2012 The β-glucan receptor dectin-1 promotes lung immunopathology during fungal allergy via IL-22. Journal of immunology (Baltimore, Md. : 1950) 119 22933634
2012 Immunomodulation of Fungal β-Glucan in Host Defense Signaling by Dectin-1. Biomolecules & therapeutics 117 24009832
2019 The macrophage tetraspan MS4A4A enhances dectin-1-dependent NK cell-mediated resistance to metastasis. Nature immunology 115 31263276
2018 An increase in LRRK2 suppresses autophagy and enhances Dectin-1-induced immunity in a mouse model of colitis. Science translational medicine 112 29875204
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 106 31926564
2014 Nonagonistic Dectin-1 ligand transforms CpG into a multitask nanoparticulate TLR9 agonist. Proceedings of the National Academy of Sciences of the United States of America 100 24516163
2012 Relative contributions of dectin-1 and complement to immune responses to particulate β-glucans. Journal of immunology (Baltimore, Md. : 1950) 93 22649195
2012 Dectin-1 isoforms contribute to distinct Th1/Th17 cell activation in mucosal candidiasis. Cellular & molecular immunology 90 22543832
2006 Expression of functionally different dectin-1 isoforms by murine macrophages. Journal of immunology (Baltimore, Md. : 1950) 90 16622020
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2014 Dectin-1 is expressed in human lung and mediates the proinflammatory immune response to nontypeable Haemophilus influenzae. mBio 81 25161190
2008 Fungal Recognition by TLR2 and Dectin-1. Handbook of experimental pharmacology 79 18071656
2023 Dectin-1 signaling on colonic γδ T cells promotes psychosocial stress responses. Nature immunology 76 36941398
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
2011 Mycobacterium abscessus activates the NLRP3 inflammasome via Dectin-1-Syk and p62/SQSTM1. Immunology and cell biology 73 21876553
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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
2013 Dectin-1 activation controls maturation of β-1,3-glucan-containing phagosomes. The Journal of biological chemistry 67 23609446
2009 Internalization of Dectin-1 terminates induction of inflammatory responses. European journal of immunology 67 19130473
2014 Innate immunity induced by fungal β-glucans via dectin-1 signaling pathway. International journal of medicinal mushrooms 66 24940900
2010 PPARγ controls Dectin-1 expression required for host antifungal defense against Candida albicans. PLoS pathogens 64 20062524
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2008 The pattern recognition receptor Dectin-1: from fungi to mycobacteria. Current drug targets 58 18288963
2009 Barley-derived beta-D-glucan induces immunostimulation via a dectin-1-mediated pathway. Immunology letters 52 19428562
2018 Dysregulated invertebrate tropomyosin-dectin-1 interaction confers susceptibility to allergic diseases. Science immunology 51 29475849
2016 Particulate β-glucans synergistically activate TLR4 and Dectin-1 in human dendritic cells. Molecular nutrition & food research 51 27358258
2021 Inhibition of Dectin-1 Ameliorates Neuroinflammation by Regulating Microglia/Macrophage Phenotype After Intracerebral Hemorrhage in Mice. Translational stroke research 50 33539006
2021 Emerging roles of Dectin-1 in noninfectious settings and in the CNS. Trends in immunology 50 34489167
2014 Dectin-1 activation induces proliferation and migration of human keratinocytes enhancing wound re-epithelialization. Cellular immunology 47 24721111
2022 Galectin 3 enhances platelet aggregation and thrombosis via Dectin-1 activation: a translational study. European heart journal 46 35165707
2009 Glucocorticoid receptor agonist compound K regulates Dectin-1-dependent inflammatory signaling through inhibition of reactive oxygen species. Life sciences 45 19733186
2016 Dectin-1 Controls TLR9 Trafficking to Phagosomes Containing β-1,3 Glucan. Journal of immunology (Baltimore, Md. : 1950) 44 26829985
2011 Fungal recognition enhances mannose receptor shedding through dectin-1 engagement. The Journal of biological chemistry 44 21205820
2008 Costimulation of dectin-1 and DC-SIGN triggers the arachidonic acid cascade in human monocyte-derived dendritic cells. Journal of immunology (Baltimore, Md. : 1950) 44 18390758
2019 Dectin-1-induced RIPK1 and RIPK3 activation protects host against Candida albicans infection. Cell death and differentiation 43 30944411
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2010 Dectin-1: a role in antifungal defense and consequences of genetic polymorphisms in humans. Mammalian genome : official journal of the International Mammalian Genome Society 42 20700596
2023 Cancer immunotherapy via synergistic coactivation of myeloid receptors CD40 and Dectin-1. Science immunology 41 37976347
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
2018 Interleukin-33 Contributes to the Induction of Th9 Cells and Antitumor Efficacy by Dectin-1-Activated Dendritic Cells. Frontiers in immunology 40 30108595
2023 β-amyloid binds to microglia Dectin-1 to induce inflammatory response in the pathogenesis of Alzheimer's disease. International journal of biological sciences 38 37416769
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2023 Dectin-1 Acts as a Non-Classical Receptor of Ang II to Induce Cardiac Remodeling. Circulation research 37 36786193
2024 Genetic variants of dectin-1 and their antifungal immunity impact in hematologic malignancies: A comprehensive systematic review. Current research in translational medicine 36 39038414
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2017 Characterization of C-type lectins reveals an unexpectedly limited interaction between Cryptococcus neoformans spores and Dectin-1. PloS one 36 28282442
2021 Microfilariae Trigger Eosinophil Extracellular DNA Traps in a Dectin-1-Dependent Manner. Cell reports 35 33440150
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2016 Polymorphisms of Dectin-1 and TLR2 Predispose to Invasive Fungal Disease in Patients with Acute Myeloid Leukemia. PloS one 34 26963509
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2022 Phagosomal signalling of the C-type lectin receptor Dectin-1 is terminated by intramembrane proteolysis. Nature communications 31 35388002
2022 Regulating microglial miR-155 transcriptional phenotype alleviates Alzheimer's-induced retinal vasculopathy by limiting Clec7a/Galectin-3+ neurodegenerative microglia. Acta neuropathologica communications 31 36076283
2018 β-Glucan-induced cooperative oligomerization of Dectin-1 C-type lectin-like domain. Glycobiology 31 29897456
2020 Inhibition of Dectin-1 in mice ameliorates cardiac remodeling by suppressing NF-κB/NLRP3 signaling after myocardial infarction. International immunopharmacology 30 31978804
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 30 31754039
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
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2014 The role of Human Dectin-1 Y238X Gene Polymorphism in recurrent vulvovaginal candidiasis infections. Molecular biology reports 26 25008994
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2017 Dectin-1 intracellular domain determines species-specific ligand spectrum by modulating receptor sensitivity. The Journal of biological chemistry 25 28848046
2019 The Core Fucose on an IgG Antibody is an Endogenous Ligand of Dectin-1. Angewandte Chemie (International ed. in English) 24 31625659
2017 Isoform localization of Dectin-1 regulates the signaling quality of anti-fungal immunity. European journal of immunology 24 28303575
2014 Induction and activation of human Th17 by targeting antigens to dendritic cells via dectin-1. Journal of immunology (Baltimore, Md. : 1950) 24 24835401
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2017 The Absence of NOD1 Enhances Killing of Aspergillus fumigatus Through Modulation of Dectin-1 Expression. Frontiers in immunology 23 29326692
2024 The Dectin-1 and Dectin-2 clusters: C-type lectin receptors with fundamental roles in immunity. EMBO reports 22 39482490
2019 Dectin-1 genetic deficiency predicts chronic lung allograft dysfunction and death. JCI insight 22 31613800
2023 Immunoglobulin G-dependent inhibition of inflammatory bone remodeling requires pattern recognition receptor Dectin-1. Immunity 21 36948194
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2024 Clec7a Worsens Long-Term Outcomes after Ischemic Stroke by Aggravating Microglia-Mediated Synapse Elimination. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 19 39088351