Affinage

CLEC5A

C-type lectin domain family 5 member A · UniProt Q9NY25

Length
188 aa
Mass
21.5 kDa
Annotated
2026-06-09
64 papers in source corpus 25 papers cited in narrative 25 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CLEC5A (MDL-1/CLECSF5) is a type II transmembrane C-type lectin on myeloid and endothelial cells that functions as a pattern-recognition receptor coupling pathogen and damage signals to proinflammatory myeloid activation (PMID:10449773, PMID:18496526). It lacks an intrinsic signaling motif and instead transduces signals through non-covalent association with the ITAM-bearing adaptor DAP12 via a charged transmembrane residue, with cooperative recruitment of DAP10, triggering calcium mobilization and a Syk/PI3K/Akt cascade that in immature myeloid cells drives NO and TNF-α production through Akt-activated eNOS (PMID:10449773, PMID:19251634, PMID:22005300). As a receptor, homodimeric CLEC5A recognizes terminal fucose/mannose glycans on flavivirus virions, influenza hemagglutinin, and GlcNAc/MurNAc disaccharides of bacterial peptidoglycan, and engages platelet-derived extracellular vesicles in concert with TLR2 (PMID:21566123, PMID:27795434, PMID:28824166, PMID:31160588, PMID:32152943). Through these ligands CLEC5A drives proinflammatory cytokine release, NLRP3 inflammasome activation and pyroptosis, neutrophil extracellular trap formation, and vascular barrier dysfunction across dengue, Zika, influenza, SARS-CoV-2, bacterial, and sepsis models, where its genetic or antibody-mediated blockade reduces inflammation and improves survival (PMID:18496526, PMID:23152543, PMID:28824166, PMID:31160588, PMID:35820906, PMID:40498836). CLEC5A additionally promotes osteoclastogenesis and inflammatory bone erosion in arthritis and colitis, and its transcription is controlled by the myeloid factor PU.1 and induced by Nrf2 during viral infection (PMID:19251634, PMID:20212065, PMID:36787107, PMID:35835390, PMID:21094529, PMID:27561946).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1999 High

    Established CLEC5A as a myeloid activating receptor by showing it has no intrinsic signaling capacity but couples to the ITAM adaptor DAP12 to mobilize calcium, defining the core signaling logic.

    Evidence Molecular cloning, co-association assay and calcium mobilization in J774 macrophages

    PMID:10449773

    Open questions at the time
    • Endogenous ligand unknown at this stage
    • Downstream effector cascade beyond calcium not defined
  2. 2008 High

    Identified the first physiological context for CLEC5A as a flavivirus sensor, showing direct dengue virion binding triggers DAP12 phosphorylation and pathogenic cytokine release driving plasma leakage in vivo.

    Evidence Direct binding assay, DAP12 phosphorylation, anti-CLEC5A blockade and STAT1-deficient mouse model

    PMID:18496526

    Open questions at the time
    • Precise glycan ligand on virion not yet resolved
    • Cofactor requirements for low-avidity engagement unaddressed
  3. 2009 High

    Expanded the receptor complex to a trimolecular MDL-1–DAP12/DAP10 assembly and linked CLEC5A signaling to osteoclastogenesis, broadening its role beyond infection to bone homeostasis.

    Evidence Co-immunoprecipitation, in vitro osteoclastogenesis and DAP10-knockout mouse phenotyping

    PMID:19251634

    Open questions at the time
    • Ligand driving osteoclast-context activation unclear
    • Relative signaling contributions of DAP12 vs DAP10 not dissected
  4. 2010 High

    Demonstrated CLEC5A as a pathogenic driver of inflammatory arthritis and defined its transcriptional control by PU.1, connecting receptor expression to myeloid lineage programming.

    Evidence Mdl1 knockout and MDL-1-Ig blockade in arthritis model; ChIP and promoter reporter for PU.1 binding

    PMID:20212065 PMID:21094529

    Open questions at the time
    • Endogenous arthritis-relevant ligand not identified
    • Additional transcriptional regulators not explored
  5. 2011 High

    Provided structural and mechanistic detail by solving the crystal structure revealing a homodimer with a conformational binary switch, and dissected the DAP12/DAP10/Syk/PI3K/Akt/eNOS cascade leading to shock.

    Evidence X-ray crystallography with MD/glycan array/docking; in vivo ConA liver injury with co-IP and pharmacological pathway dissection

    PMID:21566123 PMID:22005300

    Open questions at the time
    • How extracellular conformational change is transmitted to DAP12 not directly demonstrated
    • eNOS-vs-iNOS branching context dependence incompletely mapped
  6. 2012 High

    Linked CLEC5A to inflammasome biology by showing it is required for dengue-induced NLRP3 activation, caspase-1-dependent IL-1β/IL-18 release and pyroptosis selectively in inflammatory macrophages.

    Evidence Anti-CLEC5A blockade, caspase-1 and cytokine assays in GM-CSF vs M-CSF macrophages

    PMID:23152543

    Open questions at the time
    • Molecular link between CLEC5A signaling and NLRP3 assembly not resolved
    • Reason for macrophage-subset specificity unexplained
  7. 2016 Medium

    Broadened ligand recognition to influenza hemagglutinin and defined how viral infection feeds back to upregulate CLEC5A via PERK/Nrf2 ER stress, and how virus engages CLEC5A cooperatively with MR/DC-SIGN.

    Evidence Lectin screen, siRNA/blockade and CLEC5A-KO H5N1 infection; Nrf2 translocation and NS2B3 forced expression; co-IP and proximity binding with MR/DC-SIGN

    PMID:27561946 PMID:27795434 PMID:27832191

    Open questions at the time
    • MR/DC-SIGN hetero-complex model partly inferred from binding data
    • Nrf2 axis from single lab
  8. 2017 High

    Established CLEC5A as a bacterial sensor recognizing peptidoglycan GlcNAc/MurNAc and required for NET formation and antibacterial defense, generalizing its pattern-recognition role beyond viruses.

    Evidence Clec5a-/- Listeria infection model with NET, ROS, cytokine and histopathology readouts

    PMID:28824166

    Open questions at the time
    • Structural basis of disaccharide recognition not solved
    • Contribution to other bacterial infections untested
  9. 2019 High

    Defined a platelet–EV–CLEC5A/TLR2 axis whereby virus-activated platelets release vesicles that co-engage CLEC5A and TLR2 to drive NETosis, and consolidated dual carbohydrate ligand specificity.

    Evidence EV functional assays, dual antibody blockade and clec5a-/-/tlr2-/- double-KO dengue mouse survival; review of glycan specificity

    PMID:31160588 PMID:32152943

    Open questions at the time
    • EV cargo recognized by CLEC5A not identified
    • Mechanism of CLEC5A–TLR2 cooperation undefined
  10. 2022 High

    Extended the EV/CLEC5A/TLR2 NETosis axis to SARS-CoV-2 thromboinflammation and demonstrated CLEC5A as the essential driver of IL-23-induced and colitis-associated osteoclastogenesis and bone destruction.

    Evidence clec5a-/-/tlr2-/- COVID lung inflammation model; IL-23 gene transfer with micro-CT and MDL-1-KO; colitis models with anti-MDL-1 antibody

    PMID:35820906 PMID:35835390 PMID:36787107

    Open questions at the time
    • Whether the same EV ligands operate across diseases unconfirmed
    • Direct osteoclast-precursor activating ligand unidentified
  11. 2023 High

    Confirmed DAP12 as the obligate signaling partner for CLEC5A-driven tissue pathology in vivo by showing dap12-/- mice phenocopy clec5a-/- mice in Zika-induced testicular inflammation.

    Evidence Clec5a-/- and dap12-/- ZIKV infection models with histology, viral titer and sperm function readouts

    PMID:36803804

    Open questions at the time
    • Glycan ligand on ZIKV not specified
    • Cell type initiating testicular damage not isolated
  12. 2025 High

    Identified an endothelial role for CLEC5A in vascular barrier dysfunction and an epigenetic mechanism (DNMT1/CpG demethylation) driving monocyte CLEC5A overexpression and NF-κB-dependent atherogenic inflammation.

    Evidence Endothelial-specific knockdown with rescue in CLP sepsis plus barrier/adhesion assays; methylome–transcriptome integration with DNMT1/folic acid in ApoE-/- model

    PMID:40147659 PMID:40498836

    Open questions at the time
    • Endothelial CLEC5A ligand and DAP12 dependence in endothelium not defined
    • Atherosclerosis epigenetic axis from single lab
  13. 2024 Medium

    Revealed context-dependent and tissue-protective or regulatory roles for CLEC5A, including restraint of microglial Aβ clearance, a TREM1–NLRC4 pyroptosis axis, and tolerogenic DC immunomodulation.

    Evidence Clec5a-/- AD crosses with phagocytosis assays; CLEC5A–TREM1 co-IP and knockdown in SCI; Clec5a knockdown tolDCs in PD model

    PMID:39187376 PMID:39443966 PMID:40917058

    Open questions at the time
    • CLEC5A–TREM1 interaction rests on single co-IP without reciprocal validation
    • Mechanism of Aβ clearance restraint not defined
    • tolDC immunomodulation from single study

Open questions

Synthesis pass · forward-looking unresolved questions
  • How extracellular ligand binding and the homodimer conformational switch are mechanistically transmitted across the membrane to control DAP12/DAP10 ITAM signaling, and whether distinct ligands evoke distinct downstream programs, remains unresolved.
  • No structure of a CLEC5A–DAP12 signaling complex
  • Ligand-specific signaling outcomes not directly compared
  • Determinants of pro- vs anti-inflammatory outcomes in different tissues unknown

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:0140299 molecular sensor activity 3 GO:0008289 lipid binding 2
Localization
GO:0005886 plasma membrane 3
Pathway
R-HSA-168256 Immune System 4 R-HSA-5357801 Programmed Cell Death 3 R-HSA-162582 Signal Transduction 2
Partners
DAP10DAP12REEP5TLR2TREM1
Complex memberships
CLEC5A–DAP12 complexCLEC5A–DAP12–DAP10 trimolecular complex

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 CLEC5A (MDL-1) is a type II transmembrane C-type lectin that associates non-covalently with DAP12 via a charged residue in its transmembrane region; crosslinking of MDL-1/DAP12 complexes on macrophages results in calcium mobilization, establishing a myeloid cell activation pathway. Molecular cloning, co-association assay, calcium mobilization assay in J774 macrophage cells Proceedings of the National Academy of Sciences of the United States of America High 10449773
2008 CLEC5A directly interacts with dengue virions (without viral entry) and triggers DAP12 phosphorylation, stimulating proinflammatory cytokine release from macrophages; blockade of CLEC5A suppresses cytokine secretion and reduces DV-induced plasma leakage and mortality in STAT1-deficient mice without affecting IFN-α release. Direct binding assay (CLEC5A–dengue virion interaction), DAP12 phosphorylation assay, anti-CLEC5A monoclonal antibody blockade, in vivo STAT1-deficient mouse model Nature High 18496526
2009 MDL-1 (CLEC5A) associates with both DAP12 and DAP10 in osteoclasts and bone marrow-derived macrophages, forming trimolecular MDL-1–DAP12/DAP10 complexes; DAP10 association depends almost entirely on DAP12. MDL-1-mediated stimulation augments osteoclastogenesis in vitro, and DAP10-deficient mice become osteopetrotic with reduced osteoclasts. Co-immunoprecipitation, in vitro osteoclastogenesis assay, DAP10-knockout mouse phenotype analysis Proceedings of the National Academy of Sciences of the United States of America High 19251634
2010 MDL-1 (CLEC5A) activation enhances recruitment of inflammatory macrophages and neutrophils to joints and promotes bone erosion in autoimmune arthritis; genetic deletion of Mdl1 or treatment with MDL-1-Ig fusion protein reduces clinical signs of joint inflammation. Mdl1 gene deletion (knockout mice), MDL-1-Ig fusion protein treatment, autoimmune arthritis model The Journal of experimental medicine High 20212065
2010 CLEC5A expression in monocytes/macrophages and granulocytes is transcriptionally regulated by the myeloid transcription factor PU.1, which binds directly to the CLEC5A promoter in vivo. Microarray profiling, PU.1 knockdown/restoration, CLEC5A promoter reporter assay, chromatin immunoprecipitation (ChIP) for PU.1 binding Molecular immunology High 21094529
2011 CLEC5A is homodimeric at the cell surface. A crystal structure (1.9 Å) revealed a β-sheet extension acting as a binary switch regulating molecular flexibility; extracellular conformational changes may be transmitted through the membrane to influence DAP12 signaling. CLEC5A binds dengue virus serotypes 1–4. X-ray crystallography (1.9 Å), molecular dynamics simulations, glycan microarray, docking studies, cell-surface binding experiments The Journal of biological chemistry High 21566123
2011 Activation of MDL-1 (CLEC5A) on immature CD11b+Gr-1+Ly6G+Ly6C+ myeloid cells triggers NO and TNF-α production via a DAP12/DAP10/Syk/PI3K/Akt/eNOS (not iNOS) signaling cascade, leading to shock; Akt physically interacts with and activates eNOS in this pathway. In vivo ConA liver injury model, MDL-1 agonist antibody treatment, MDL-1+ cell depletion, genetic knockouts, co-immunoprecipitation (Akt–eNOS interaction), pharmacological inhibition of Syk/PI3K/Akt The Journal of clinical investigation High 22005300
2012 CLEC5A is required for dengue virus-induced NLRP3 inflammasome activation and caspase-1-dependent IL-1β/IL-18 secretion and pyroptosis in GM-CSF-polarized (inflammatory) macrophages; blockade of CLEC5A inhibits NLRP3 inflammasome activation and pyroptosis. Anti-CLEC5A antibody blockade, caspase-1 activation assay, IL-1β/IL-18 ELISA, pyroptosis readout in GM-Mφ vs M-Mφ Blood High 23152543
2016 CLEC5A interacts with the hemagglutinin protein of influenza viruses; CLEC5A-mediated signaling enhances proinflammatory cytokine (TNF-α, IP-10) production in macrophages without affecting viral replication; CLEC5A-deficient macrophages show elevated IFN-α and upregulated TLR3 after dsRNA treatment; CLEC5A-deficient mice show reduced lung inflammation and improved survival after lethal H5N1 challenge. Lectin screening identifying HA–CLEC5A interaction, siRNA silencing, anti-CLEC5A antibody blockade, Syk inhibitor, CLEC5A-KO mouse infection model Journal of virology High 27795434
2016 Dengue virus infection activates Nrf2 via PERK-mediated ER stress, which drives transcriptional upregulation of CLEC5A; elevated CLEC5A then enhances TLR3-independent TNF-α production; the DENV NS2B3 protein is sufficient to induce Nrf2 nuclear translocation and CLEC5A expression. Nrf2 nuclear translocation assay, PERK inhibition, CLEC5A promoter activation, NS2B3 forced expression, TNF-α ELISA, in vivo mouse brain analysis Scientific reports Medium 27561946
2016 Dengue virus–CLEC5A interaction forms a multivalent hetero-complex with the mannose receptor (MR)/DC-SIGN on macrophages: MR/DC-SIGN first captures virus with high avidity, enabling low-avidity CLEC5A to engage virus in close proximity and initiate signaling. Co-immunoprecipitation, proximity-based binding assays, blocking experiments with anti-MR/DC-SIGN antibodies PloS one Medium 27832191
2017 CLEC5A is required for neutrophil extracellular trap (NET) formation, ROS production, and proinflammatory cytokine (IL-1β, IL-17A, TNF) release in response to Listeria monocytogenes; Clec5a-/- mice show rapid bacterial dissemination, severe liver necrosis, and increased mortality, and CLEC5A engages bacterial peptidoglycan (GlcNAc/MurNAc disaccharides). Clec5a-/- mouse infection model, NET formation assay, ROS measurement, cytokine ELISA, liver histopathology, flow cytometry Nature communications High 28824166
2019 Dengue virus activates platelets via CLEC2 to release extracellular vesicles (exosomes and microvesicles); these EVs activate CLEC5A and TLR2 on neutrophils and macrophages, inducing NET formation and proinflammatory cytokine release; simultaneous blockade of CLEC5A and TLR2 increases survival from 30% to 90% in dengue-infected stat1-/- mice. EV isolation and characterization, anti-CLEC5A/anti-TLR2 antibody blockade, NET formation assay, clec5a-/-/tlr2-/- double-KO mouse model, survival analysis Nature communications High 31160588
2022 SARS-CoV-2-activated platelets produce extracellular vesicles that induce NET formation via CLEC5A and TLR2 on neutrophils; simultaneous genetic ablation of CLEC5A and TLR2 (clec5a-/-/tlr2-/- mice) dramatically attenuates SARS-CoV-2-induced lung thromboinflammation in vivo. EV isolation from COVID-19 patient sera, anti-CLEC5A/anti-TLR2 antibody blockade, clec5a-/-/tlr2-/- double-KO mouse model, NET formation assay, in vivo lung inflammation assessment Journal of biomedical science High 35820906
2023 CLEC5A mediates Zika virus-induced testicular inflammation; in clec5a-/-/stat1-/- mice, ZIKV-induced testicular inflammation, neutrophil infiltration, and sperm damage are reduced; CLEC5A-associated DAP12 signaling regulates ZIKV-induced testicular damage, as dap12-/-/stat1-/- mice phenocopy clec5a-/- mice. Clec5a-/- and dap12-/- KO mouse ZIKV infection model, immunohistochemistry, qRT-PCR for viral titer, cytokine measurement, spermatozoa counting/motility Journal of biomedical science High 36803804
2022 IL-23 induces expansion of a myeloid MDL-1+CD11b+Ly6G+ osteoclast precursor population; genetic ablation of MDL-1 (CLEC5A) completely prevents IL-23-induced osteoclastogenesis and bone destruction in inflammatory arthritis; MDL-1-/- mice have increased bone mineral density. In vivo IL-23 gene transfer, spectral flow cytometry, micro-CT bone analysis, Western blotting, immunoprecipitation, MDL-1-KO mouse osteoclastogenesis assay Arthritis & rheumatology High 36787107
2022 MDL-1 (CLEC5A) on osteoclast precursors is upregulated during intestinal inflammation; anti-MDL-1 antibody treatment abrogates enhanced osteoclast differentiation ex vivo and ameliorates bone loss during colitis in vivo. Multiple murine colitis models, anti-MDL-1 antibody treatment, ex vivo osteoclast differentiation assay, flow cytometry, micro-CT Cellular and molecular gastroenterology and hepatology High 35835390
2025 Endothelial CLEC5A drives vascular barrier dysfunction in sepsis; endothelial-specific knockdown of CLEC5A improves survival and reduces vascular leakage in CLP-challenged mice; in vitro, CLEC5A deletion maintains trans-endothelial electrical resistance and inhibits monocyte/neutrophil adhesion and trans-endothelial migration under LPS stimulation. Endothelial-specific CLEC5A knockdown, CLEC5A re-expression rescue, CLP sepsis mouse model, single-cell RNA sequencing, trans-endothelial electrical resistance assay, monocyte/neutrophil adhesion and migration assays Science advances High 40498836
2021 CLEC5A knockdown in a myocardial infarction model suppresses macrophage M1 polarization, NLRP3 inflammasome activation, pyroptosis, and NF-κB signaling in the left ventricle; in vitro, CLEC5A knockdown inhibits LPS/IFNγ-stimulated M1 polarization in RAW264.7 cells and blocks polarized macrophage-induced NLRP3/pyroptosis in co-cultured cardiomyocytes. In vivo adenoviral shRNA knockdown, mouse MI model, in vitro co-culture, Western blot for NLRP3/caspase-1/NF-κB, macrophage polarization assay Biochemistry and cell biology Medium 33939927
2024 Clec5a knockout microglia show enhanced phagocytosis of Aβ; in AD mice, Clec5a knockout reduces Aβ deposition, increases microglia coverage around plaques, and ameliorates memory deficits; CLEC5A normally restrains microglial Aβ clearance. Clec5a-/- × AD mouse model crosses, Morris water maze, ELISA for Aβ, immunohistochemistry, fluorescent-labeled Aβ phagocytosis assay in knockdown microglial lines and KO primary microglia Journal of neuroinflammation Medium 39443966
2024 CLEC5A interacts with TREM1; this interaction mediates NLRC4 expression and thereby promotes neuronal pyroptosis in a spinal cord injury model; knockdown of CLEC5A, TREM1, or NLRC4 attenuates pyroptosis markers (LDH, GSDMD-N, caspase-1, IL-1β, IL-18). Co-immunoprecipitation (CLEC5A–TREM1 interaction), siRNA knockdown in PC12 cells and in vivo rat SCI model, Western blot for pyroptosis markers eNeuro Medium 39187376
2025 CLEC5A epigenetic upregulation via DNMT1-mediated demethylation of CpG site cg06744540 drives CLEC5A overexpression in monocytes/macrophages; elevated CLEC5A activates NF-κB signaling to enhance inflammation, migration, adhesion, macrophage polarization, lipid accumulation, and inhibit apoptosis; folic acid increases DNMT1 expression, reduces CLEC5A, and suppresses atherosclerotic plaque formation in vivo. Methylome–transcriptome integration, DNMT1 overexpression, CpG site mapping, NF-κB pathway analysis, functional assays (migration, adhesion, lipid accumulation), high-fat ApoE-/- mouse model International journal of biological macromolecules Medium 40147659
2024 In tolerogenic dendritic cells (tolDCs), Clec5a promotes IL-10 production and Foxp3+ Treg induction while suppressing NF-κB signaling and IL-6; Clec5a-knockdown tolDCs show reduced immunomodulatory function; administration of Clec5a-expressing DCs ameliorates dopaminergic neuron loss, reduces α-synuclein accumulation, and improves locomotor behavior in MPTP-induced PD mice. Clec5a knockdown in tolDCs, cytokine ELISA (IL-10, IL-6), Foxp3+ Treg quantification, NF-κB signaling assay, MPTP mouse model, immunohistochemistry Frontiers in bioscience (Landmark edition) Medium 40917058
2019 CLEC5A binds fucose and mannose moieties of dengue virus membrane glycans, as well as GlcNAc/MurNAc disaccharides of bacterial cell walls, establishing its dual ligand-recognition properties as a pattern recognition receptor. Glycan binding assays, structural analyses reviewed in the context of prior crystallography and binding studies Advances in experimental medicine and biology Medium 32152943
2059 REEP5 physically binds CLEC5A and its overexpression abolishes CLEC5A-induced ER stress-mediated apoptosis in cardiomyocytes, placing REEP5 as a negative regulator of CLEC5A-driven cardiac cell death. Co-immunoprecipitation (REEP5–CLEC5A interaction), REEP5 overexpression in hypoxia-induced cardiomyocyte model, ER stress markers (PERK, IRE1α, ATF6, CHOP, caspase-12), in vivo MI mouse model BMC cardiovascular disorders Low 39044150

Source papers

Stage 0 corpus · 64 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 CLEC5A is critical for dengue-virus-induced lethal disease. Nature 329 18496526
2019 Extracellular vesicles from CLEC2-activated platelets enhance dengue virus-induced lethality via CLEC5A/TLR2. Nature communications 193 31160588
2012 CLEC5A is critical for dengue virus-induced inflammasome activation in human macrophages. Blood 180 23152543
1999 Myeloid DAP12-associating lectin (MDL)-1 is a cell surface receptor involved in the activation of myeloid cells. Proceedings of the National Academy of Sciences of the United States of America 170 10449773
2002 TREM-1, MDL-1, and DAP12 expression is associated with a mature stage of myeloid development. Molecular immunology 115 11922939
2017 CLEC5A is a critical receptor in innate immunity against Listeria infection. Nature communications 89 28824166
2015 CD163L1 and CLEC5A discriminate subsets of human resident and inflammatory macrophages in vivo. Journal of leukocyte biology 82 25877931
2010 Myeloid DAP12-associating lectin (MDL)-1 regulates synovial inflammation and bone erosion associated with autoimmune arthritis. The Journal of experimental medicine 79 20212065
2019 CLEC2 and CLEC5A: Pathogenic Host Factors in Acute Viral Infections. Frontiers in immunology 63 31867016
2009 Signal adaptor DAP10 associates with MDL-1 and triggers osteoclastogenesis in cooperation with DAP12. Proceedings of the National Academy of Sciences of the United States of America 59 19251634
2011 Activation of MDL-1 (CLEC5A) on immature myeloid cells triggers lethal shock in mice. The Journal of clinical investigation 54 22005300
2016 Activation of Nrf2 by the dengue virus causes an increase in CLEC5A, which enhances TNF-α production by mononuclear phagocytes. Scientific reports 49 27561946
2016 CLEC5A-Mediated Enhancement of the Inflammatory Response in Myeloid Cells Contributes to Influenza Virus Pathogenicity In Vivo. Journal of virology 48 27795434
2022 CLEC5A and TLR2 are critical in SARS-CoV-2-induced NET formation and lung inflammation. Journal of biomedical science 45 35820906
2016 Dengue Virus Infection Is through a Cooperative Interaction between a Mannose Receptor and CLEC5A on Macrophage as a Multivalent Hetero-Complex. PloS one 45 27832191
2011 Structural flexibility of the macrophage dengue virus receptor CLEC5A: implications for ligand binding and signaling. The Journal of biological chemistry 41 21566123
1998 The C. elegans MDL-1 and MXL-1 proteins can functionally substitute for vertebrate MAD and MAX. Oncogene 40 9764821
2010 CLEC5A (MDL-1) is a novel PU.1 transcriptional target during myeloid differentiation. Molecular immunology 34 21094529
2020 CLEC5A: A Promiscuous Pattern Recognition Receptor to Microbes and Beyond. Advances in experimental medicine and biology 32 32152943
2008 Expression and functional role of MDL-1 (CLEC5A) in mouse myeloid lineage cells. Journal of leukocyte biology 30 19074552
2016 Cutting Edge: CLEC5A Mediates Macrophage Function and Chronic Obstructive Pulmonary Disease Pathologies. Journal of immunology (Baltimore, Md. : 1950) 29 26927798
2014 MDL-1, a growth- and tumor-suppressor, slows aging and prevents germline hyperplasia and hypertrophy in C. elegans. Aging 29 24531613
2019 CLEC5A expressed on myeloid cells as a M2 biomarker relates to immunosuppression and decreased survival in patients with glioma. Cancer gene therapy 26 31591460
2019 C-type lectin domain family 5, member A (CLEC5A, MDL-1) promotes brain glioblastoma tumorigenesis by regulating PI3K/Akt signalling. Cell proliferation 21 30834619
2023 Interleukin-23 Regulates Inflammatory Osteoclastogenesis via Activation of CLEC5A(+) Osteoclast Precursors. Arthritis & rheumatology (Hoboken, N.J.) 20 36787107
2020 CLEC5A promotes the proliferation of gastric cancer cells by activating the PI3K/AKT/mTOR pathway. Biochemical and biophysical research communications 20 32033754
2022 Intestinal Inflammation Promotes MDL-1+ Osteoclast Precursor Expansion to Trigger Osteoclastogenesis and Bone Loss. Cellular and molecular gastroenterology and hepatology 19 35835390
2022 Activation of the Innate Immune Checkpoint CLEC5A on Myeloid Cells in the Absence of Danger Signals Modulates Macrophages' Function but Does Not Trigger the Adaptive T Cell Immune Response. Journal of immunology research 18 35252461
2021 CLEC5A knockdown protects against cardiac dysfunction after myocardial infarction by suppressing macrophage polarization, NLRP3 inflammasome activation, and pyroptosis. Biochemistry and cell biology = Biochimie et biologie cellulaire 18 33939927
2014 Nanostructured electrochemical biosensor for th0065 detection of the weak binding between the dengue virus and the CLEC5A receptor. Nanomedicine : nanotechnology, biology, and medicine 18 24674971
2014 A potential role of myeloid DAP12-associating lectin (MDL)-1 in the regulation of inflammation in rheumatoid arthritis patients. PloS one 17 24465901
2017 The macrophage C-type lectin receptor CLEC5A (MDL-1) expression is associated with early plaque progression and promotes macrophage survival. Journal of translational medicine 16 29126450
2020 Elevated Expression of C-Type Lectin Domain Family 5-Member A (CLEC5A) and Its Relation to Inflammatory Parameters and Disease Course in Adult-Onset Still's Disease. Journal of immunology research 15 32377540
2019 Transcription factor CEBPB inhibits the proliferation of osteosarcoma by regulating downstream target gene CLEC5A. Journal of clinical laboratory analysis 15 31364785
2021 Activation of an Effective Immune Response after Yellow Fever Vaccination Is Associated with the Genetic Background and Early Response of IFN-γ and CLEC5A. Viruses 13 33445752
2023 Phellopterin attenuates ovarian cancer proliferation and chemoresistance by inhibiting the PU.1/CLEC5A/PI3K-AKT feedback loop. Toxicology and applied pharmacology 12 37708916
2017 Association of rs1285933 single nucleotide polymorphism in CLEC5A gene with dengue severity and its functional effects. Human immunology 12 28764923
2024 The influence of CLEC5A on early macrophage-mediated inflammation in COPD progression. Cellular and molecular life sciences : CMLS 11 39097839
2023 CLEC5A mediates Zika virus-induced testicular damage. Journal of biomedical science 10 36803804
2024 IL-23 induces CLEC5A+ IL-17A+ neutrophils and elicit skin inflammation associated with psoriatic arthritis. Journal of autoimmunity 9 38301504
2025 Endothelial CLEC5A drives barrier dysfunction and vascular leakage responsible for lung injury in bacterial pneumonia and sepsis. Science advances 8 40498836
2023 CLEC5A expression can be triggered by spike glycoprotein and may be a potential target for COVID-19 therapy. Journal of medical virology 7 36571274
1982 A new genetic variation of the malate dehydrogenase-like enzyme (MDL-1) in inbred rats and its possible linkage. Biochemical genetics 7 7115281
2024 The deficient CLEC5A ameliorates the behavioral and pathological deficits via the microglial Aβ clearance in Alzheimer's disease mouse model. Journal of neuroinflammation 6 39443966
2022 In Silico Design of siRNAs for Silencing CLEC5A Receptor as a Potential Therapeutic Approach Against Dengue and Japanese Encephalitis Virus Infection in Human. Bioinformatics and biology insights 6 36530559
2009 Crystallization and X-ray diffraction analysis of human CLEC5A (MDL-1), a dengue virus receptor. Acta crystallographica. Section F, Structural biology and crystallization communications 6 20057064
2020 Genetic association analysis of CLEC5A and CLEC7A gene single-nucleotide polymorphisms and Crohn's disease. World journal of gastroenterology 5 32476786
2023 CLEC5A regulates the proliferation and migration of colon cancer via the AKT/mTOR signaling pathway. Journal of gastrointestinal oncology 4 37435201
2023 In-Silico CLEC5A mRNA expression analysis to predict Dengue susceptibility in cancer patients. Biochemistry and biophysics reports 3 37415850
2023 Polymorphisms in CLEC5A and CLEC7A genes modify risk for inflammatory bowel disease. Annals of gastroenterology 3 38223252
2011 Lack of association between CLEC5A gene single-nucleotide polymorphisms and Kawasaki disease in Taiwanese children. Journal of biomedicine & biotechnology 3 22536019
2025 Epigenetic upregulation of CLEC5A contributes to monocyte/macrophage dysfunction in coronary artery disease. International journal of biological macromolecules 2 40147659
2005 [Study on the interaction mechanism of antibacterial peptide MDL-1 in Musca domestica L and E. coli DNA by fluorescence spectra]. Guang pu xue yu guang pu fen xi = Guang pu 2 16013322
2025 CLEC5A suppresses cell growth and metastasis via interfering with the calcineurin/NFATc1 signaling pathway in osteosarcoma. Experimental cell research 1 40516779
2025 CLEC5A Activation in Inflammatory Monocytes: A Mechanism for Enhanced Adaptive Immunity Following COVID-19 mRNA Vaccination in a Preclinical Study. Viruses 1 41012661
2025 Causal inference of CLEC5A and ISG20 in atherosclerosis: integrating Mendelian randomization and eQTL evidence. Frontiers in immunology 1 41415292
2024 REEP5 mediates the function of CLEC5A to alleviate myocardial infarction by inhibiting endoplasmic reticulum stress-induced apoptosis. BMC cardiovascular disorders 1 39044150
2024 CLEC5A Promotes Neuronal Pyroptosis in Rat Spinal Cord Injury Models by Interacting with TREM1 and Elevating NLRC4 Expression. eNeuro 1 39187376
2022 CLEC5a-directed bispecific antibody for effective cellular phagocytosis. mAbs 1 35293277
2026 The protective role of MDL-1 in sepsis-induced lung injury: insights from a murine CLP model. Frontiers in immunology 0 41890760
2026 Single-Cell Profiling Identifies CLEC5A+ Macrophages as Key Drivers of Thoracic Aortic Aneurysm Via CCL5-Mediated M1 Polarization. Journal of clinical laboratory analysis 0 42011731
2025 Dendritic Cells Induce Clec5a-mediated Immune Modulation in MPTP-induced Parkinson's Disease Mouse Model. Frontiers in bioscience (Landmark edition) 0 40917058
2025 CLEC5A Knockdown Reduces Oxidative Stress and Inflammation Caused by Lipopolysaccharide in Renal Tubular Epithelial Cells via the NF-κB/NLRP3 Signaling Pathway. Archivum immunologiae et therapiae experimentalis 0 41172238
2023 [Overexpression of CLEC5A inhibits cell proliferation and metastasis and reverses epithelial-mesenchymal transition in hepatocellular carcinoma]. Nan fang yi ke da xue xue bao = Journal of Southern Medical University 0 36856214

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