Affinage

CLEC6A

C-type lectin domain family 6 member A · UniProt Q6EIG7

Length
209 aa
Mass
24.0 kDa
Annotated
2026-06-09
100 papers in source corpus 31 papers cited in narrative 31 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

CLEC6A (Dectin-2) is a myeloid C-type lectin pattern-recognition receptor that detects high-mannose glycan structures on fungi and other microbes to initiate innate and adaptive immune responses (PMID:16423983, PMID:20493731). Its Ca2+-dependent carbohydrate-recognition domain binds Manα1-2Man epitopes via a primary site for reducing-end mannose and an adjacent secondary site for terminal mannose, a geometry that confers selectivity for fungal α-mannans, mycobacterial mannose-capped lipoarabinomannan, bacterial mannosylated O-antigens, and Aspergillus galactomannan (PMID:28652405, PMID:25176311, PMID:27358401, PMID:36598192). Lacking an intracellular signaling motif, Dectin-2 associates with the FcRγ chain and signals through Syk kinase and the CARD9-Bcl10-Malt1 module, selectively activating the NF-κB subunit c-Rel together with PLCγ2 and PI3Kδ/PKCδ to drive IL-1β, IL-23, TNF-α, and cysteinyl leukotriene production (PMID:17050534, PMID:19703985, PMID:21283787, PMID:22041900, PMID:27194783). Through these outputs Dectin-2 polarizes Th17 and Th2 responses, triggers NLRP3 inflammasome activation, and promotes NADPH-oxidase-independent NET formation, collectively mediating antifungal host defense against Candida albicans and other pathogens (PMID:20493731, PMID:21357742, PMID:31693704, PMID:28671985). Receptor signaling is initiated by ligand-induced crosslinking of Dectin-2 dimers, whose CRDs are oriented by the neck region to favor clustering of FcRγ (PMID:39361900), and signaling avidity is enhanced by heterodimerization with Dectin-3/MCL for α-mannan recognition (PMID:23911656). Beyond microbial sensing, Dectin-2 on Kupffer cells acts as a phagocytic 'eat me' receptor for cancer cells within an ERMAP-galectin-9-Dectin-2 bridging complex to suppress liver metastasis (PMID:27872290, PMID:37813965), and drives osteoclastogenesis through a Syk/NOX2/ROS/MAPK axis (PMID:39800085). A homozygous human loss-of-function deletion abolishes surface clustering and cytokine responses to A. fumigatus, establishing the receptor's nonredundant role in human antifungal immunity (PMID:33733279).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2000 Medium

    Establishing that Dectin-2 is a dendritic-cell-restricted type II transmembrane C-type lectin defined its lineage and structural class before any ligand or function was known.

    Evidence Subtractive cDNA cloning, RT-PCR, and genomic analysis identifying 6 exons and alternatively spliced isoforms

    PMID:10766825

    Open questions at the time
    • No ligand identified
    • No signaling mechanism defined
    • Function of truncated isoforms unknown
  2. 2006 High

    Identifying that the CRD binds high-mannose structures in a cation-dependent manner and preferentially recognizes fungal hyphae, while the receptor itself recruits FcRγ for signaling, defined both the ligand class and the requirement for an adaptor chain.

    Evidence Glycan array and competitive binding with soluble CRD, co-IP with FcRγ, NF-κB reporter, Src inhibition, cytokine ELISA

    PMID:16423983 PMID:17050534

    Open questions at the time
    • Downstream kinase identity not yet placed
    • Structural basis of mannose selectivity not resolved
  3. 2009 High

    Demonstrating that Dectin-2 couples through FcRγ to Syk and CARD9 to drive dendritic cell activation and Th17 responses, and to generate cysteinyl leukotrienes, established the core signaling axis and its adaptive immune output.

    Evidence Genetic knockout/blockade, Syk assays, CARD9 epistasis, lentiviral knockdown, FcRγ-/- BMDCs, T cell cytokine assays, fungal infection

    PMID:19124755 PMID:19703985

    Open questions at the time
    • Selectivity among NF-κB subunits not yet defined
    • PLCγ2 and PI3K branch not yet placed
  4. 2010 High

    Mapping the Syk-CARD9-Bcl10-NF-κB pathway in a Clec4n-/- mouse and showing it drives IL-1β/IL-23 and Th17 differentiation, with extension to schistosome antigen-driven NLRP3 inflammasome activation, established Dectin-2 as a master integrator of innate-to-adaptive signaling.

    Evidence Clec4n-/- mice, cytokine ELISA, IKK ubiquitination/phosphorylation assays, CARD9-Bcl10 co-IP, ROS and K+ efflux measurement, Nlrp3/ASC KO mice

    PMID:20493731 PMID:20538615 PMID:21059925

    Open questions at the time
    • Which NF-κB subunit is selectively engaged not resolved
    • Quantitative contribution of distinct ligands to inflammasome activation unclear
  5. 2011 High

    Resolving that Dectin-2 selectively activates the c-Rel NF-κB subunit via CARD9-Bcl10-Malt1, uses PLCγ2 (not PLCγ1), and engages a cys-LT-CysLT1R axis for Th2 immunity refined the signaling specificity underlying distinct T-helper outcomes.

    Evidence Malt1 inhibition, c-Rel activation assays, PLCγ2-/- vs PLCγ1-/- macrophages, LTC4S-/- and CysLT1R-/- mice, adoptive transfer, lung inflammation assays

    PMID:21283787 PMID:21357742 PMID:22041900

    Open questions at the time
    • How a single receptor branches between Th17 and Th2 outputs not fully resolved
    • PI3Kδ/PKCδ node not yet placed
  6. 2013 High

    Demonstrating constitutive Dectin-3/Dectin-2 heterodimers that bind α-mannans more effectively than homodimers revealed combinatorial CLR assembly as a mechanism to tune ligand avidity and signaling strength.

    Evidence Dectin-3 KO mice, heterodimerization analysis, α-mannan binding comparison, NF-κB reporter, in vivo candidiasis

    PMID:23911656

    Open questions at the time
    • Stoichiometry and structural arrangement of heterodimer not defined
    • Human relevance of heterodimer not addressed here
  7. 2014 High

    Establishing Dectin-2 as a direct receptor for mycobacterial mannose-capped lipoarabinomannan with adjuvant and EAE-driving activity extended its ligand repertoire beyond fungi to bacterial glycans and autoimmune contexts.

    Evidence Clec4n-/- BMDC cytokine assays, direct binding, antigen-specific T cell assays, EAE and mycobacterial infection models

    PMID:25176311

    Open questions at the time
    • Structural basis of Man-LAM recognition not yet defined
    • Contribution to in vivo TB control not quantified
  8. 2016 High

    Placing PI3Kδ downstream of Syk to control PKCδ and both leukotriene and cytokine output, identifying mannosylated bacterial O-antigens and TLR4 cross-talk, and revealing a Kupffer-cell-restricted phagocytic anti-metastatic function broadened both the signaling map and the physiological roles of Dectin-2.

    Evidence PI3Kδ inhibition/knockdown with epistasis, reporter assays with O-antigen ligands and CRD mutants, Dectin-2-/- liver metastasis model, cell-type-specific phagocytosis assays

    PMID:27194783 PMID:27358401 PMID:27872290

    Open questions at the time
    • Mechanism conferring phagocytic competence specifically on Kupffer cells unresolved
    • Cancer-cell ligand not yet identified
  9. 2017 High

    Solving the CRD-Man9GlcNAc2 crystal structure with primary and secondary Ca2+-coordinated mannose sites explained selectivity for Manα1-2Man-containing glycans, and identification of an endogenous β-glucuronidase self-ligand plus Histoplasma-driven NLRP3 activation expanded the receptor's recognition scope.

    Evidence X-ray crystallography with ligand, mutagenesis, glycan array; reporter assay with Gusb identification; receptor-deficient DCs with caspase-1/cathepsin B analysis

    PMID:28046067 PMID:28652405 PMID:28671985

    Open questions at the time
    • Physiological role of self-ligand recognition unclear
    • Gusb interaction is single-lab Medium-confidence
  10. 2019 High

    Dissecting a Syk-Ca2+-PKCδ-PAD4 axis driving NADPH-oxidase-independent NETosis and a Dectin-2-Syk-NLRP3 pathway propagating vascular inflammation linked receptor signaling to specific effector programs in neutrophils and vessel-wall macrophages.

    Evidence Dectin-2-/- mice, PAD4/Syk/PKCδ inhibitors, NE translocation imaging, CAWS vasculitis model, intravital imaging, NLRP3 and CCL2/CCR2 analysis

    PMID:31169521 PMID:31693704

    Open questions at the time
    • Trigger distinguishing NETosis versus cytokine output not defined
    • Human relevance of vasculitis mechanism not established
  11. 2023 High

    Identifying the ERMAP-galectin-9-Dectin-2 trimeric bridging complex as a glycosylation-dependent 'eat me' signal and confirming Dectin-2 as a galactomannan receptor defined a non-microbial phagocytic role and a new fungal ligand.

    Evidence Genome-wide CRISPR screen, co-IP of trimeric complex, glycosylation-dependent interaction and phagocytosis assays, liver metastasis model; galactomannan binding and signaling assays with Dectin-2-/- aspergillosis model

    PMID:36598192 PMID:37813965

    Open questions at the time
    • Structural basis of the trimeric bridging complex not resolved
    • How galectin-9 bridges ERMAP to Dectin-2 mechanistically unclear
  12. 2024 High

    Crystal structures of the extended extracellular domain showed that neck-region-stabilized dimers orient sugar-binding sites for ligand-induced crosslinking and FcRγ clustering, providing the structural mechanism of signal initiation, while N-mannan-driven trained immunity revealed a memory function.

    Evidence X-ray crystallography of extended ectodomain, disulfide-variant and TM-replacement analyses, sugar-binding geometry; C. albicans mannosylation mutants and trained immunity protocols

    PMID:38446996 PMID:39361900

    Open questions at the time
    • Threshold of clustering required for signaling not quantified
    • Epigenetic basis of Dectin-2-driven trained immunity not defined
  13. 2025 Medium

    Demonstrating Dectin-2-driven osteoclastogenesis via a Syk/NOX2/ROS/MAPK axis with reduced bone resorption in KO mice extended the receptor's role to non-immune bone remodeling and periodontitis.

    Evidence siRNA knockdown, overexpression, pathway inhibition, single-cell sequencing, Dectin-2 KO periodontitis model, histology

    PMID:39800085

    Open questions at the time
    • Activating ligand in osteoclast context not identified
    • Single-lab finding without independent replication

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how a single receptor selects between divergent effector outcomes (Th17 versus Th2, cytokine versus NETosis, microbial defense versus phagocytic clearance) and what governs human-specific differences in CLR heterodimerization.
  • Determinants of branching among downstream effector programs unknown
  • Human MCL does not heterodimerize with Dectin-2, complicating cross-species extrapolation
  • Endogenous self-ligand physiology uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0001618 virus receptor activity 4 GO:0060089 molecular transducer activity 3 GO:0038024 cargo receptor activity 2 GO:0005198 structural molecule activity 1
Localization
GO:0005886 plasma membrane 3
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-168256 Immune System 3 R-HSA-5653656 Vesicle-mediated transport 2
Partners
BCL10CARD9CLEC4DERMAPFCER1GLGALS9PLCG2SYK
Complex memberships
CARD9-Bcl10-Malt1 signaling moduleDectin-2/Dectin-3(MCL) heterodimerDectin-2/FcRγ receptor complexERMAP-galectin-9-Dectin-2 bridging complex

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 Dectin-2 (CLEC6A) was cloned as a type II transmembrane C-type lectin expressed in a dendritic cell-specific manner; genomic analysis revealed it is encoded by 6 exons, with two truncated isoforms (beta and gamma) produced by alternative splicing. Subtractive cDNA cloning, RT-PCR, immunoblotting, genomic analysis The Journal of biological chemistry Medium 10766825
2006 Dectin-2 binds preferentially to hyphal (rather than yeast/conidial) components of Candida albicans and other fungi; it lacks an intracellular signaling motif and instead associates with the FcRγ chain, whose ligation leads to protein tyrosine phosphorylation, NF-κB activation, ligand internalization, and TNF-α/IL-1Ra secretion, all blocked by the Src kinase inhibitor PP2. Binding assays with soluble dectin-2 receptor, co-immunoprecipitation with FcRγ, NF-κB reporter assay, Src kinase inhibition, cytokine ELISA The Journal of biological chemistry High 17050534
2006 The carbohydrate-recognition domain (CRD) of Dectin-2 is a C-type lectin that binds high-mannose structures (Man9GlcNAc2) in a cation-dependent manner, with selectivity for mannose/fucose-like sugars; binding to C. albicans and zymosan is abrogated by cation chelation and competed by yeast mannans. Competitive inhibition binding assays, glycan array analysis, live C. albicans binding assays with soluble CRD fusion protein Glycobiology High 16423983
2009 Dectin-2 signals via Syk kinase and the adaptor CARD9, coupling to Syk indirectly through association with the FcRγ chain (unlike Dectin-1 which has an ITAM-like motif); this pathway is required for dendritic cell activation and Th17 responses to Candida albicans. Genetic knockout/blockade experiments, Syk kinase assays, CARD9 epistasis, T cell cytokine assays, fungal infection model The Journal of experimental medicine High 19703985
2009 Dectin-2 mediates cysteinyl leukotriene (cys-LT) generation from dendritic cells in response to house dust mite and Aspergillus fumigatus glycans; this requires FcRγ chain and Syk kinase, and was confirmed by lentiviral knockdown of Dectin-2 in bone marrow-derived DCs. Lentiviral knockdown, FcRγ-/- BMDCs, Syk inhibitors, transfection of individual receptors in mast cells, cys-LT ELISA Journal of immunology High 19124755
2010 Dectin-2 recognizes fungal alpha-mannans and signals through FcRγ chain and a Syk-CARD9-NF-κB-dependent pathway (without MAP kinase involvement) to induce IL-1β and IL-23 secretion; this pathway is required for Th17 cell differentiation and host defense against C. albicans. Clec4n-/- mouse generation, cytokine ELISA, signaling pathway analysis, T helper differentiation assays, in vivo candidiasis model Immunity High 20493731
2010 Schistosoma mansoni soluble egg antigens bind the Dectin-2/FcRγ complex and activate the Syk kinase signaling pathway, inducing reactive oxygen species and potassium efflux, which activates the Nlrp3 inflammasome leading to IL-1β production. Dectin-2/FcRγ complex binding assays, Syk activation assays, ROS measurement, K+ efflux assay, Nlrp3/ASC KO mice, IL-1β ELISA Proceedings of the National Academy of Sciences of the United States of America High 21059925
2010 CARD9 is selectively involved in Dectin-2-induced NF-κB activation in response to C. albicans hyphae; it mediates IκBα kinase ubiquitination (while Syk regulates IκBα kinase phosphorylation), and promotes CARD9-Bcl10 association downstream of Dectin-2 but not Dectin-1. Dectin-2 siRNA knockdown, CARD9 overexpression/KD, IKK ubiquitination assays, IKK phosphorylation assays, NF-κB reporter, co-IP of CARD9-Bcl10 The Journal of biological chemistry High 20538615
2011 Dectin-2 mediates Th2 immunity through Dectin-2-dependent cysteinyl leukotriene generation; this pathway requires LTC4 synthase and CysLT1R, establishing the Dectin-2–cys-LT–CysLT1R axis as critical for eosinophilic pulmonary inflammation and Th2 cytokine production. Lentiviral KD of Dectin-2, adoptive transfer of pulsed BMDCs, LTC4S-/- and CysLT1R-/- mice, cytokine ELISA, lung inflammation assays The Journal of experimental medicine High 21357742
2011 Dectin-2 activates the NF-κB subunit c-Rel selectively (rather than all NF-κB subunits) through the CARD9-Bcl10-Malt1 signaling module in human dendritic cells, driving Th17-polarizing cytokines IL-1β and IL-23p19; Malt1 inhibition abrogates this c-Rel activation. Malt1 inhibitor treatment, c-Rel activation assays, dectin-2 stimulation of human DCs, cytokine ELISA, NF-κB subunit analysis PLoS pathogens High 21283787
2011 PLCγ2 functions downstream of Dectin-2 in response to C. albicans hyphae; PLCγ2-deficient (but not PLCγ1-deficient) macrophages show defective NF-κB and MAPK activation, reduced ROS production, and impaired cytokine production; PLCγ2-/- mice are defective in clearing C. albicans in vivo. PLCγ2-/- and PLCγ1-/- macrophages, NF-κB/MAPK activation assays, ROS assay, cytokine ELISA, in vivo candidiasis model The Journal of biological chemistry High 22041900
2013 Dectin-3 (CLECSF8/MCL/Clec4d) constitutively forms heterodimers with Dectin-2; the Dectin-3/Dectin-2 heterodimer binds α-mannans on C. albicans hyphae more effectively than respective homodimers, leading to potent NF-κB activation and inflammatory responses. Dectin-3 genetic KO mice, heterodimerization analysis, α-mannan binding assays, NF-κB reporter, cytokine assays, in vivo candidiasis model Immunity High 23911656
2014 Dectin-2 is a direct receptor for mannose-capped lipoarabinomannan (Man-LAM) of Mycobacterium tuberculosis; Man-LAM-induced cytokine production by BMDCs is completely abrogated in Clec4n-/- mice, and Dectin-2 mediates antigen-specific T cell responses and experimental autoimmune encephalomyelitis adjuvant activity through Man-LAM recognition. Clec4n-/- BMDC cytokine assays, direct binding experiments, antigen-specific T cell assays, EAE model in Clec4n-/- mice, in vivo mycobacterial infection Immunity High 25176311
2015 Dectin-2 (but not Dectin-1) participates in Aspergillus fumigatus hyphal recognition by human plasmacytoid dendritic cells, acting in cooperation with the FcRγ chain to trigger signaling responses leading to TNF-α and IFN-α release, antifungal activity, and pDC extracellular trap (pET) formation containing DNA and citrullinated histone H3. Dectin-2 blockade in human pDCs, cytokine ELISA, confocal and electron microscopy of pET formation, microarray transcriptome analysis PLoS pathogens High 25659141
2017 The crystal structure of the human Dectin-2 CRD in complex with Man9GlcNAc2 revealed a primary Ca2+-coordinated binding site for reducing-end mannose and an adjacent secondary site for terminal non-reducing mannose; this geometry accommodates Manα1-2Man in internal positions of mannans, explaining selectivity for fungal mannans, bacterial LPS, and lipoarabinomannans containing Manα1-2Man. X-ray crystallography of CRD-oligosaccharide complex, competition binding studies, glycan array analysis, mutagenesis of binding site residues The Journal of biological chemistry High 28652405
2016 Dectin-2 functions in Kupffer cells (liver-resident macrophages) to mediate phagocytosis and clearance of cancer cells, suppressing liver metastasis; this phagocytic activity is selectively conferred on Kupffer cells (not bone marrow-derived or alveolar macrophages), and MCL (macrophage C-type lectin) also contributes to this function. Dectin-2-/- mouse liver metastasis model, phagocytosis assays in different macrophage populations, subcutaneous tumor and lung metastasis controls Proceedings of the National Academy of Sciences of the United States of America High 27872290
2016 PI3Kδ acts as a common upstream requirement downstream of Syk in the Dectin-2 signaling pathway, regulating protein kinase Cδ activity and controlling Dectin-2-dependent generation of both cysteinyl leukotrienes and cytokines (IL-23, IL-6, TNF-α, IL-33) in dendritic cells. Pharmacological PI3Kδ inhibition, siRNA knockdown, Dectin-2 cross-linking, adoptive transfer model, in vivo PI3Kδ inhibitor administration Journal of immunology High 27194783
2016 Dectin-2 recognizes mannosylated O-antigens of Gram-negative bacteria (Hafnia alvei, E. coli O9a); binding requires the carbohydrate-recognition domain of Dectin-2 (abrogated by CRD mutations and mannosidase treatment), and Dectin-2 cross-talk with TLR4 involves Syk activation and receptor juxtaposition to augment cytokine production. Cell-based reporter assay, mannosidase treatment, Dectin-2 CRD binding-site mutants, Syk activation assay, Dectin-2 KO BMDCs, cytokine ELISA The Journal of biological chemistry High 27358401
2017 Dectin-2 recognizes an endogenous self-ligand: β-glucuronidase (Gusb) expressed on dendritic cells; binding requires mannose-binding motif in Dectin-2 and N-glycosylation sites in Gusb; overexpression of Gusb confers ability to stimulate Dectin-2 reporter cells. Dectin-2 reporter cell assay, mannose competition, Dectin-2 mannose-binding motif mutant, Gusb identification by pulldown, N-glycosylation site mutagenesis, Gusb overexpression PloS one Medium 28046067
2018 ManLAM from M. tuberculosis is the sole ligand mediating bacilli recognition by Dectin-2; (α1→2)-linked mannoside caps are required for signaling; lipoglycans from other bacterial species bearing α1→2 mannosides are also Dectin-2 ligands; dimannoside caps and multivalent interactions are required for binding and signaling. Isogenic M. tuberculosis mutant strains, Dectin-2 reporter signaling assay, synthetic mannodendrimers and lipoglycan variants, competitive inhibition binding Scientific reports High 30443026
2019 Dectin-2 recognizes unopsonized C. albicans and mediates NADPH oxidase-independent NETosis in neutrophils through activation of the downstream Syk-Ca2+-PKCδ-PAD4 signaling pathway, which modulates nuclear translocation of neutrophil elastase and histone citrullination; dectin-2-mediated NET formation in vivo restrains C. albicans dissemination. Dectin-2-/- mice, PAD4 inhibitor (GSK484), Syk/Ca2+/PKCδ pathway inhibitors, confocal microscopy for NE nuclear translocation, citrullinated histone assay, in vivo peritonitis model with DNase treatment PLoS pathogens High 31693704
2019 Dectin-2 signaling in macrophages resident in the aortic root induces CCL2 production, recruiting CCR2+ inflammatory monocytes that differentiate into monocyte-derived DCs in the vessel wall; these DCs release IL-1β via a Dectin-2-Syk-NLRP3 inflammasome pathway, which then activates endothelial cells to express CXCL1/CCL2 and adhesion molecules, propagating vascular inflammation in a KD-like model. Dectin-2-/- mice in CAWS-vasculitis model, intravital imaging, CCL2/CCR2 pathway analysis, NLRP3 inflammasome activation assays, monocyte adoptive transfer, IL-1β blockade The Journal of clinical investigation High 31169521
2017 Dectin-2 promotes NLRP3 inflammasome activation as a primary receptor in dendritic cells responding to Histoplasma capsulatum; Dectin-2 and Dectin-1 trigger Syk-JNK to activate both signal 1 (pro-IL-1β synthesis) and signal 2 (caspase-1 activation); cathepsin B release (regulated by ERK/JNK downstream of these receptors) serves as signal 2. Receptor-deficient DCs from Clec4n-/-, Clec7a-/-, and double KO mice, reciprocal receptor blockade, caspase-1 activation assays, K+ efflux measurement, cathepsin B inhibition, JNK/ERK pathway analysis PLoS pathogens High 28671985
2023 ERMAP on cancer cells interacts with galectin-9 on Kupffer cells, which forms a bridging complex with Dectin-2 on Kupffer cells to induce phagocytosis of cancer cells; this ERMAP-galectin-9-Dectin-2 axis functions as an 'eat me' signal controlling liver metastasis. In vivo genome-wide CRISPR-Cas9 KO screen, co-immunoprecipitation of ERMAP-galectin-9-Dectin-2 complex, glycosylation-dependent interaction assays, phagocytosis assays, liver metastasis mouse model Nature immunology High 37813965
2023 Dectin-2 is a receptor for Aspergillus fumigatus galactomannan; galactomannan binds Dectin-2 and induces Dectin-2-dependent signaling including Syk activation, gene transcription, and TNF-α production; Dectin-2 deficiency increases immune cell recruitment to lungs but is dispensable for survival in pulmonary aspergillosis. Fungal-like particles with purified galactomannan, Dectin-2 binding assay, Syk phosphorylation assay, NF-κB/gene transcription reporter, TNF-α ELISA, Dectin-2-/- mouse aspergillosis model mBio High 36598192
2024 Crystal structure and biochemical analysis revealed that Dectin-2 and BDCA-2 form dimers in which CRDs have only limited direct interaction but are stabilized by the neck region; the resulting orientation of sugar-binding sites in dimers favors crosslinking of multiple dimers by oligosaccharide ligands, causing FcRγ clustering to initiate signaling. X-ray crystallography of extended extracellular domain of Dectin-2, disulfide-bonded BDCA-2 variant analysis, transmembrane domain replacement with dimerization domains, sugar-binding site geometry analysis Glycobiology High 39361900
2025 Dectin-2 promotes osteoclastogenesis via the Syk/NOX2/ROS/MAPK signaling axis; Dectin-2 knockdown inhibits RAW264.7 and BMDM differentiation into osteoclasts while overexpression enhances it; Dectin-2 KO mice show reduced osteoclast numbers and decreased alveolar bone resorption in periodontitis. siRNA knockdown, Dectin-2 overexpression, Syk/NOX2/ROS/MAPK pathway analysis, single-cell sequencing, Dectin-2 KO mouse periodontitis model, histology Free radical biology & medicine Medium 39800085
2003 Dectin-2 on antigen-presenting cells interacts with an unidentified ligand on regulatory T cells; a soluble Dectin-2 fusion protein (sDec2) that blocks this interaction prevents UV-induced tolerance and breaks established hapten-specific tolerance; sDec2-reactive T cells are the regulatory T cells responsible for UV-induced immunosuppression. Soluble fusion protein blockade, contact hypersensitivity model, FACS analysis of sDec2-binding T cells, adoptive transfer of tolerance Journal of immunology Medium 14500681
2021 A human Dectin-2 homozygous deletion mutation (507 del C, frameshift N170I with early stop codon) results in weakly expressed protein that does not form cell-surface clusters and is functionally defective; patient PBMCs carrying this mutation fail to produce TNF-α and IL-6 in response to A. fumigatus. Genetic sequencing of patient DNA, flow cytometry for Dectin-2 surface expression/clustering, cytokine ELISA from patient PBMCs The Journal of infectious diseases Medium 33733279
2022 Human MCL and Mincle form a disulfide-linked heterodimer that associates with FcεRIγ, but human MCL does not form a heterodimer with Dectin-2 (in contrast to findings in mouse and rat), indicating species differences in CLR heterodimerization. Co-transfection experiments, flow cytometry, co-immunoprecipitation Scandinavian journal of immunology Medium 35194806
2024 N-linked mannans (but not O-linked mannans) of C. albicans cell wall potentiate the induction of trained immunity (innate immune memory), and this process is mediated by Dectin-2; branching of N-linked mannan is essential for this effect. C. albicans mannosylation mutants, cytokine assays, T-cell cytokine readouts, trained immunity induction protocol with Dectin-2-dependent pathway analysis The Journal of infectious diseases Medium 38446996

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 Dectin-2 recognition of alpha-mannans and induction of Th17 cell differentiation is essential for host defense against Candida albicans. Immunity 601 20493731
2009 Dectin-2 is a Syk-coupled pattern recognition receptor crucial for Th17 responses to fungal infection. The Journal of experimental medicine 364 19703985
2013 Activation of neutrophils by autocrine IL-17A-IL-17RC interactions during fungal infection is regulated by IL-6, IL-23, RORγt and dectin-2. Nature immunology 356 24362892
2006 Dectin-2 is a pattern recognition receptor for fungi that couples with the Fc receptor gamma chain to induce innate immune responses. The Journal of biological chemistry 350 17050534
2006 The carbohydrate-recognition domain of Dectin-2 is a C-type lectin with specificity for high mannose. Glycobiology 286 16423983
2013 C-type lectin receptors Dectin-3 and Dectin-2 form a heterodimeric pattern-recognition receptor for host defense against fungal infection. Immunity 268 23911656
2014 Dectin-2 is a direct receptor for mannose-capped lipoarabinomannan of mycobacteria. Immunity 221 25176311
2010 Schistosoma mansoni triggers Dectin-2, which activates the Nlrp3 inflammasome and alters adaptive immune responses. Proceedings of the National Academy of Sciences of the United States of America 197 21059925
2009 Dectin-2 recognition of house dust mite triggers cysteinyl leukotriene generation by dendritic cells. Journal of immunology (Baltimore, Md. : 1950) 192 19124755
2011 Dectin-1 and Dectin-2 in innate immunity against fungi. International immunology 179 21677049
2011 Dectin-2 mediates Th2 immunity through the generation of cysteinyl leukotrienes. The Journal of experimental medicine 156 21357742
2013 The RodA hydrophobin on Aspergillus fumigatus spores masks dectin-1- and dectin-2-dependent responses and enhances fungal survival in vivo. Journal of immunology (Baltimore, Md. : 1950) 142 23926321
2013 The Dectin-2 family of C-type lectin-like receptors: an update. International immunology 140 23606632
2011 Selective C-Rel activation via Malt1 controls anti-fungal T(H)-17 immunity by dectin-1 and dectin-2. PLoS pathogens 132 21283787
2015 Recognition of Aspergillus fumigatus hyphae by human plasmacytoid dendritic cells is mediated by dectin-2 and results in formation of extracellular traps. PLoS pathogens 131 25659141
2000 Cloning of a second dendritic cell-associated C-type lectin (dectin-2) and its alternatively spliced isoforms. The Journal of biological chemistry 131 10766825
2005 Dectin-2 is predominantly myeloid restricted and exhibits unique activation-dependent expression on maturing inflammatory monocytes elicited in vivo. European journal of immunology 106 15940672
2010 CARD9 mediates dectin-2-induced IkappaBalpha kinase ubiquitination leading to activation of NF-kappaB in response to stimulation by the hyphal form of Candida albicans. The Journal of biological chemistry 104 20538615
2016 The innate immune receptor Dectin-2 mediates the phagocytosis of cancer cells by Kupffer cells for the suppression of liver metastasis. Proceedings of the National Academy of Sciences of the United States of America 96 27872290
2009 The Dectin-2 family of C-type lectins in immunity and homeostasis. Cytokine 94 19665392
2019 Candida albicans triggers NADPH oxidase-independent neutrophil extracellular traps through dectin-2. PLoS pathogens 75 31693704
2017 Dectin-2 Deficiency Modulates Th1 Differentiation and Improves Wound Healing After Myocardial Infarction. Circulation research 75 28193608
2017 Mechanism of pathogen recognition by human dectin-2. The Journal of biological chemistry 73 28652405
2014 Dectin-2 promotes house dust mite-induced T helper type 2 and type 17 cell differentiation and allergic airway inflammation in mice. American journal of respiratory cell and molecular biology 67 24588637
2019 Dectin-2-induced CCL2 production in tissue-resident macrophages ignites cardiac arteritis. The Journal of clinical investigation 62 31169521
2023 The ligation between ERMAP, galectin-9 and dectin-2 promotes Kupffer cell phagocytosis and antitumor immunity. Nature immunology 61 37813965
2019 Thymic stromal lymphopoietin epigenetically upregulates Fc receptor γ subunit-related receptors on antigen-presenting cells and induces TH2/TH17 polarization through dectin-2. The Journal of allergy and clinical immunology 60 31251950
2003 Involvement of dectin-2 in ultraviolet radiation-induced tolerance. Journal of immunology (Baltimore, Md. : 1950) 58 14500681
2014 Dectin-2 deficiency promotes Th2 response and mucin production in the lungs after pulmonary infection with Cryptococcus neoformans. Infection and immunity 55 25422263
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
2013 Dectin-2 sensing of house dust mite is critical for the initiation of airway inflammation. Mucosal immunology 50 24129160
2017 Dectin-2 is a primary receptor for NLRP3 inflammasome activation in dendritic cell response to Histoplasma capsulatum. PLoS pathogens 43 28671985
2016 The Role of Dectin-2 for Host Defense Against Disseminated Candidiasis. Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research 43 27046240
2014 Dectin-2 regulates the effector phase of house dust mite-elicited pulmonary inflammation independently from its role in sensitization. Journal of immunology (Baltimore, Md. : 1950) 42 24453247
2011 Phospholipase Cγ2 (PLCγ2) is key component in Dectin-2 signaling pathway, mediating anti-fungal innate immune responses. The Journal of biological chemistry 42 22041900
2018 Deciphering the molecular basis of mycobacteria and lipoglycan recognition by the C-type lectin Dectin-2. Scientific reports 39 30443026
2005 Identification and expression profiling of a human C-type lectin, structurally homologous to mouse dectin-2. Experimental dermatology 39 15810886
2019 Dectin-2-Targeted Antifungal Liposomes Exhibit Enhanced Efficacy. mSphere 38 31666315
2006 Induction of CD8+ T cell responses through targeting of antigen to Dectin-2. Cellular immunology 37 16781694
2016 Dectin-2 Recognizes Mannosylated O-antigens of Human Opportunistic Pathogens and Augments Lipopolysaccharide Activation of Myeloid Cells. The Journal of biological chemistry 35 27358401
2004 Signaling and immune regulatory role of the dendritic cell immunoreceptor (DCIR) family lectins: DCIR, DCAR, dectin-2 and BDCA-2. Immunobiology 35 15481152
2012 Differential dependencies of monocytes and neutrophils on dectin-1, dectin-2 and complement for the recognition of fungal particles in inflammation. PloS one 34 23049859
2018 Dectin-2 Is a C-Type Lectin Receptor that Recognizes Pneumocystis and Participates in Innate Immune Responses. American journal of respiratory cell and molecular biology 32 28886250
2024 The Dectin-1 and Dectin-2 clusters: C-type lectin receptors with fundamental roles in immunity. EMBO reports 31 39482490
2019 Human thioredoxin, a damage-associated molecular pattern and Malassezia-crossreactive autoallergen, modulates immune responses via the C-type lectin receptors Dectin-1 and Dectin-2. Scientific reports 31 31371767
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
2013 Dectin-2 is predominately macrophage restricted and exhibits conspicuous expression during Aspergillus fumigatus invasion in human lung. Cellular immunology 29 23928558
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
2020 CARD9-Associated Dectin-1 and Dectin-2 Are Required for Protective Immunity of a Multivalent Vaccine against Coccidioides posadasii Infection. Journal of immunology (Baltimore, Md. : 1950) 27 32358020
2018 CD209a Synergizes with Dectin-2 and Mincle to Drive Severe Th17 Cell-Mediated Schistosome Egg-Induced Immunopathology. Cell reports 27 29386115
2021 Role of Dectin-2 in the Phagocytosis of Cryptococcus neoformans by Dendritic Cells. Infection and immunity 26 34251289
2015 Dectin-2 polymorphism associated with pulmonary cryptococcosis in HIV-uninfected Chinese patients. Medical mycology 26 26129889
2021 Antifungal Liposomes Directed by Dectin-2 Offer a Promising Therapeutic Option for Pulmonary Aspergillosis. mBio 24 33622715
2017 Fungal-derived cues promote ocular autoimmunity through a Dectin-2/Card9-mediated mechanism. Clinical and experimental immunology 24 28763100
2023 The C-Type Lectin Receptor Dectin-2 Is a Receptor for Aspergillus fumigatus Galactomannan. mBio 23 36598192
2020 Distinct Roles for Dectin-1 and Dectin-2 in Skin Wound Healing and Neutrophilic Inflammatory Responses. The Journal of investigative dermatology 23 32511980
2024 Candida albicans N-Linked Mannans Potentiate the Induction of Trained Immunity via Dectin-2. The Journal of infectious diseases 22 38446996
2013 Neither dectin-2 nor the mannose receptor is required for resistance to Coccidioides immitis in mice. Infection and immunity 22 24379281
2017 Overexpression of NLRP3, NLRC4 and AIM2 inflammasomes and their priming-associated molecules (TLR2, TLR4, Dectin-1, Dectin-2 and NFκB) in Malassezia folliculitis. Mycoses 21 28976036
2018 Dectin-2-Mediated Signaling Leads to Delayed Skin Wound Healing through Enhanced Neutrophilic Inflammatory Response and Neutrophil Extracellular Trap Formation. The Journal of investigative dermatology 20 30393083
2017 C-Type Lectin Receptor Dectin-2 Binds to an Endogenous Protein β-Glucuronidase on Dendritic Cells. PloS one 19 28046067
2019 TLR4, but Neither Dectin-1 nor Dectin-2, Participates in the Mollusk Hemocyanin-Induced Proinflammatory Effects in Antigen-Presenting Cells From Mammals. Frontiers in immunology 18 31214162
2020 Early immune response against Fonsecaea pedrosoi requires Dectin-2-mediated Th17 activity, whereas Th1 response, aided by Treg cells, is crucial for fungal clearance in later stage of experimental chromoblastomycosis. PLoS neglected tropical diseases 17 32542003
2019 Saccharomyces cerevisiae mannan induces sheep beta-defensin-1 expression via Dectin-2-Syk-p38 pathways in ovine ruminal epithelial cells. Veterinary research 17 30717800
2021 Dependence on Mincle and Dectin-2 Varies With Multiple Candida Species During Systemic Infection. Frontiers in microbiology 16 33717025
2015 Borrelia-induced cytokine production is mediated by spleen tyrosine kinase (Syk) but is Dectin-1 and Dectin-2 independent. Cytokine 16 26297607
2023 Honokiol reduces fungal burden and ameliorate inflammation lesions of Aspergillus fumigatus keratitis via Dectin-2 down-regulation. International immunopharmacology 15 36933490
2022 SOCS3 Regulates Dectin-2-Induced Inflammation in PBMCs of Diabetic Patients. Cells 15 36078084
2021 A Human Dectin-2 Deficiency Associated With Invasive Aspergillosis. The Journal of infectious diseases 15 33733279
2021 Dectin-2 mediates phagocytosis of Lactobacillus paracasei KW3110 and IL-10 production by macrophages. Scientific reports 15 34489491
2019 Polysaccharides from lichen Xanthoria parietina: 1,4/1,6-α-d-glucans and a highly branched galactomannan with macrophage stimulating activity via Dectin-2 activation. International journal of biological macromolecules 15 31078591
2019 Dectin-2-mediated signaling triggered by the cell wall polysaccharides of Cryptococcus neoformans. Microbiology and immunology 14 31544981
2019 Recognition of alpha-mannan by dectin 2 is essential for onset of Kawasaki disease-like murine vasculitis induced by Candida albicans cell-wall polysaccharide. Modern rheumatology 13 30924376
2016 Phosphoinositide 3-Kinase δ Regulates Dectin-2 Signaling and the Generation of Th2 and Th17 Immunity. Journal of immunology (Baltimore, Md. : 1950) 13 27194783
2013 Systems biology of host-mycobiota interactions: dissecting Dectin-1 and Dectin-2 signalling in immune cells with DC-ATLAS. Immunobiology 12 23932568
2013 Dectin-2-dependent NKT cell activation and serotype-specific antibody production in mice immunized with pneumococcal polysaccharide vaccine. PloS one 12 24205278
2018 Stimulation of Dectin-1 and Dectin-2 during Parenteral Immunization, but Not Mincle, Induces Secretory IgA in Intestinal Mucosa. Journal of immunology research 11 29725603
2019 Deletion of hematopoietic Dectin-2 or CARD9 does not protect against atherosclerotic plaque formation in hyperlipidemic mice. Scientific reports 10 30867470
2005 Ultraviolet-B radiation upregulates expression of dectin-2 on epidermal Langerhans cells by activating the gene promoter. Photochemistry and photobiology 9 15876128
2025 Dectin-2 depletion alleviates osteoclast-induced bone loss in periodontitis via Syk/NOX2/ROS signaling. Free radical biology & medicine 8 39800085
2022 Human macrophage C-type lectin forms a heteromeric receptor complex with Mincle but not Dectin-2. Scandinavian journal of immunology 8 35194806
2013 β-mannosyl linkages inhibit CAWS arteritis by negatively regulating dectin-2-dependent signaling in spleen and dendritic cells. Immunopharmacology and immunotoxicology 8 23981001
2024 High-mannose glycans from Schistosoma mansoni eggs are important for priming of Th2 responses via Dectin-2 and prostaglandin E2. Frontiers in immunology 7 38742105
2019 Antibody blockade of Dectin-2 suppresses house dust mite-induced Th2 cytokine production in dendritic cell- and monocyte-depleted peripheral blood mononuclear cell co-cultures from asthma patients. Journal of biomedical science 7 31861989
2024 D-galacto-D-mannan-mediated Dectin-2 activation orchestrates potent cellular and humoral immunity as a viral vaccine adjuvant. Frontiers in immunology 6 38433834
2019 Deletion of haematopoietic Dectin-2 or CARD9 does not protect from atherosclerosis development under hyperglycaemic conditions. Diabetes & vascular disease research 6 31868000
2024 Fungal chitin-binding glycoprotein induces Dectin-2-mediated allergic airway inflammation synergistically with chitin. PLoS pathogens 5 38170734
2022 Comparison of UVC Sensitivity and Dectin-2 Expression Between Malignant and Non-malignant Cells. In vivo (Athens, Greece) 5 36099100
2025 Contribution of CARD9 signaling to wound healing in skin promoted by topical administration of heat-killed Enterococcus faecalis strain KH2 and the involvement of Dectin-2. Frontiers in immunology 4 40574842
2023 Glabridin Inhibits Aspergillus fumigatus Growth and Alleviate Inflammation Mediated by Dectin-2 and NLRP3 Inflammasome. Current eye research 4 36785524
2018 Effect of purification of galactooligosaccharides derived from lactulose with Saccharomyces cerevisiae on their capacity to bind immune cell receptor Dectin-2. Food research international (Ottawa, Ont.) 4 30599920
2004 Transcriptional regulation of dectin-2 promoter in transgenic mouse. The Journal of veterinary medical science 4 15644596
2024 Interactions that define the arrangement of sugar-binding sites in BDCA-2 and dectin-2 dimers. Glycobiology 3 39361900
2023 Dectin-2 is critical for phagocyte function and resistance to Paracoccidioides brasiliensis in mice. Medical mycology 3 37960963
2022 Dectin-2 promotes house dust mite-skewed Th2 response through the activation of cDC2s. Cellular immunology 3 35717749
2021 Dectin-2-mediated initiation of immune responses caused by influenza virus hemagglutinin. Biomedical research (Tokyo, Japan) 3 33840686
2022 Effects of the Dectin-2/TNF-α Pathway on Ventricular Arrhythmia after Acute Myocardial Infarction in Mice. Evidence-based complementary and alternative medicine : eCAM 2 35990845
2025 Dectin-1 and dectin-2 drive protection against Sporothrix brasiliensis in experimental sporotrichosis. Frontiers in immunology 1 41080603
2023 Dectin-2 Deficiency Promotes Proinflammatory Cytokine Release From Macrophages and Impairs Insulin Secretion. Endocrinology 1 38038367
2023 Retracted: Effects of the Dectin-2/TNF-α Pathway on Ventricular Arrhythmia after Acute Myocardial Infarction in Mice. Evidence-based complementary and alternative medicine : eCAM 0 38125129

Missed literature

Know a paper Affinage missed for CLEC6A? Flag it for the maintainers and the community.

No submissions yet.