Affinage

LYVE1

Lymphatic vessel endothelial hyaluronic acid receptor 1 · UniProt Q9Y5Y7

Length
322 aa
Mass
35.2 kDa
Annotated
2026-04-28
100 papers in source corpus 23 papers cited in narrative 23 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

LYVE-1 is a lymphatic endothelial hyaluronan receptor of the Link superfamily that serves as a docking platform for immune cell trafficking across lymphatic vessels and as a co-receptor for growth factor signaling during lymphangiogenesis. It forms obligate disulfide-linked homodimers via Cys-201, adopting an open-scissors conformation that binds hyaluronan through a unique sliding mechanism—grabbing free HA chain-ends into a deep cleft—with ~15-fold higher affinity than monomers, and its HA-binding activity is regulated by avidity-dependent receptor clustering, autoinhibitory sialylation of O-glycans, cortical actin corralling, and redox-sensitive disulfide switching (PMID:27733683, PMID:40113779, PMID:19033446, PMID:26823460, PMID:32034091). Dendritic cells and macrophages dock to LYVE-1 via their HA glycocalyx to transit lymphatic endothelium, forming transmigratory cups that facilitate immune cell entry and CD8+ T cell priming; on perivascular macrophages, LYVE-1 engagement with smooth muscle cell HA drives MMP-9-dependent collagen regulation to maintain arterial compliance (PMID:28504698, PMID:30054204). LYVE-1 also directly binds FGF2, PDGF-BB, VEGF-A, and osteopontin, coupling to intracellular signaling cascades including PKC/ERK, Src, and JNK/c-Jun, while its ectodomain is shed by ADAM17 downstream of VEGF-A/ERK to promote lymphatic endothelial cell migration (PMID:23264596, PMID:21444752, PMID:39643970, PMID:26966180).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 1999 High

    The identification of LYVE-1 as a lymph vessel-specific HA receptor established the first molecular distinction between lymphatic and blood vascular endothelium and opened the question of how HA transport and signaling occur in lymphatics.

    Evidence Molecular cloning, recombinant HA-binding assays, and immunolocalization by immunofluorescence and immunoelectron microscopy

    PMID:10037799

    Open questions at the time
    • No structural information on the HA-binding mode
    • Functional role in vivo unknown
    • Signaling capacity not addressed
  2. 2001 High

    Demonstration that LYVE-1 acts as an endocytic receptor for HA, distributed on both luminal and abluminal lymphatic surfaces, established it as an active HA uptake mediator rather than merely a passive adhesion molecule.

    Evidence Transfection of 293T cells with murine LYVE-1, HA internalization assays, immunoelectron microscopy of lymphatic vessels

    PMID:11278811

    Open questions at the time
    • Endocytic pathway and sorting signals not defined
    • Physiological relevance of HA uptake not tested in vivo
  3. 2006 High

    A comprehensive LYVE-1 knockout revealed unexpectedly normal lymphatic morphology, HA homeostasis, and DC trafficking under baseline conditions, raising the question of functional redundancy versus context-dependent activation.

    Evidence Targeted gene replacement in mice with multiple functional assays including HA quantification, DC trafficking, and tumor models

    PMID:17101772

    Open questions at the time
    • Compensatory mechanisms (e.g., CD44) not fully dissected
    • Inflammatory or stress-dependent phenotypes not comprehensively explored
  4. 2007 High

    The finding that TNFα/β drive rapid internalization and degradation of LYVE-1 in inflamed lymphatics showed that receptor surface availability is dynamically regulated by inflammatory cytokines, explaining context-dependent function.

    Evidence Primary LEC culture with cytokine treatment, flow cytometry, lysosomal inhibitors, in vivo murine allergen model

    PMID:17884820

    Open questions at the time
    • Trafficking route and sorting signals for internalization undefined
    • Whether internalization serves a signaling versus clearance function unknown
  5. 2008 High

    Discovery that autoinhibitory sialylation of O-glycans silences LYVE-1 HA binding on LECs, reversible by neuraminidase, revealed a glycan-based gating mechanism that explains why the receptor is not constitutively active despite high surface expression.

    Evidence Transfection into multiple cell lines, glycosylation site mutagenesis, glycosylation-defective cell lines, neuraminidase treatment and HA-binding assays

    PMID:19033446

    Open questions at the time
    • Identity of the sialyltransferase(s) responsible not determined
    • Physiological signals that trigger desialylation in vivo unknown
  6. 2009 High

    Mapping the HA-binding surface to six key residues and showing that dimerization is required for efficient binding established the structural basis for LYVE-1's low intrinsic affinity and its dependence on avidity, distinguishing it mechanistically from CD44.

    Evidence Site-directed and truncation mutagenesis, recombinant ectodomain binding assays, BRET dimerization measurements

    PMID:19887450

    Open questions at the time
    • No atomic-resolution structure yet available
    • How dimerization is regulated in vivo unresolved
  7. 2009 Medium

    LYVE-1/CD44 double-knockout mice showed enhanced inflammatory edema compared to single knockouts, providing genetic evidence for overlapping HA receptor functions in inflammation and partially explaining the mild single-KO phenotype.

    Evidence Double-KO mice, carrageenan-induced paw edema model, intravital microscopy

    PMID:19170073

    Open questions at the time
    • Other compensating HA receptors not excluded
    • Mechanism of edema regulation not molecularly defined
  8. 2011 High

    Identification of LYVE-1 (as CRSBP-1) as a co-receptor for PDGF-BB and VEGF-A that disrupts VE-cadherin junctions via PDGFβR/β-catenin phosphorylation expanded the receptor's role from HA binding to growth factor signaling and junctional permeability regulation.

    Evidence Co-immunoprecipitation, Transwell permeability assay, kinase inhibitors, FITC-dextran injection in WT and Crsbp1-null mice

    PMID:21444752

    Open questions at the time
    • Stoichiometry and direct binding interface between LYVE-1 and PDGFβR not resolved
    • Whether this pathway operates in all lymphatic beds unclear
  9. 2012 High

    Demonstration of direct FGF2 binding to LYVE-1 with higher affinity than HA, and its requirement for FGF2-induced lymphangiogenesis, established LYVE-1 as a multi-ligand co-receptor for angiogenic growth factors beyond the HA axis.

    Evidence AlphaScreen and surface-immobilization binding assays, siRNA knockdown, in vivo corneal lymphangiogenesis

    PMID:23264596

    Open questions at the time
    • FGF2 binding site on LYVE-1 not structurally mapped
    • Relationship between FGF2 and HA binding (competitive or cooperative) not defined
  10. 2014 Medium

    LMW-HA-induced activation of PKCα/βII and ERK1/2 signaling through LYVE-1 in LECs, blocked by neutralizing antibodies, placed LYVE-1 upstream of intracellular kinase cascades that drive lymphangiogenic cell behaviors.

    Evidence Primary LEC culture, anti-LYVE-1 antibody blockade, western blotting for phospho-PKC and phospho-ERK, tube formation and migration assays

    PMID:24667755

    Open questions at the time
    • Direct signaling adapter linking LYVE-1 cytoplasmic tail to PKC/ERK not identified
    • Single-lab finding without independent replication
  11. 2015 Medium

    Cooperative signaling between LYVE-1 and S1P3 in LMW-HA-mediated lymphangiogenesis, via Src and ERK1/2, revealed LYVE-1 participates in receptor crosstalk beyond its own cytoplasmic signaling capacity.

    Evidence Co-immunoprecipitation, siRNA knockdown of LYVE-1 or S1P3, phospho-Src and phospho-ERK western blot, tube formation assay

    PMID:26116468

    Open questions at the time
    • Whether LYVE-1–S1P3 interaction is direct or scaffold-mediated not determined
    • Single-lab finding
  12. 2016 High

    Three concurrent studies resolved the biophysical mechanism of LYVE-1 HA binding: obligate Cys-201 disulfide homodimerization provides a redox-labile switch controlling affinity; avidity-dependent clustering above a threshold density is required for binding on native LECs; and VEGF-A/ERK-driven ADAM17 shedding of the ectodomain promotes LEC migration.

    Evidence Mutagenesis of Cys-201 with SAXS structural analysis and binding kinetics; divalent antibody cross-linking and HA multimerization assays; cleavage site mapping with uncleavable mutant and ADAM17 inhibitor studies

    PMID:26823460 PMID:26966180 PMID:27733683

    Open questions at the time
    • Physiological redox signals controlling the Cys-201 switch unidentified
    • Signals that cluster LYVE-1 above the threshold in vivo unknown
    • Fate and function of shed ectodomain in vivo not defined
  13. 2017 High

    In vivo demonstration that DCs dock to LYVE-1 via their HA glycocalyx and form transmigratory cups for lymphatic entry, with LYVE-1 deletion delaying DC trafficking and blunting CD8+ T cell priming, established the first non-redundant immune function for LYVE-1 that the earlier KO had missed.

    Evidence Intravital microscopy, Lyve1 gene-targeted deletion, antibody blockade, hyaluronidase treatment of DC HA coat, adoptive DC transfer, T cell priming assays

    PMID:28504698

    Open questions at the time
    • Whether all DC subsets use this pathway equally unclear
    • Structural basis of transmigratory cup formation not resolved
  14. 2018 High

    LYVE-1+ perivascular macrophages were shown to prevent arterial stiffness by engaging smooth muscle cell HA and inducing MMP-9-dependent collagen regulation, extending LYVE-1 function from lymphatic biology to vascular homeostasis.

    Evidence Aortic macrophage profiling, Csf1r deletion, MMP-9 activity assays, macrophage–SMC co-culture, arterial stiffness measurements

    PMID:30054204

    Open questions at the time
    • Whether LYVE-1 engagement directly triggers MMP-9 secretion or acts indirectly not resolved
    • Relevance to human arterial disease not established
  15. 2020 High

    Super-resolution imaging revealed that cortical actin corrals regulate LYVE-1 lateral diffusion and clustering, constraining HA-binding capacity independently of direct cytoplasmic tail–actin interactions, adding a cytoskeletal layer to the avidity-gating model.

    Evidence STED microscopy, fluorescence correlation spectroscopy, single-particle tracking, co-IP with actin, actin-disrupting drugs in primary LECs

    PMID:32034091

    Open questions at the time
    • Identity of linker proteins mediating indirect actin coupling unknown
    • How cytokine signals remodel actin corrals to activate LYVE-1 not defined
  16. 2020 Medium

    NFAT-dependent transcription of LYVE-1 was demonstrated, with FK506 suppressing LYVE-1 expression and HA uptake, linking calcineurin/NFAT signaling to lymphatic HA clearance.

    Evidence Luciferase reporter with NFAT-site mutagenesis, western blot, flow cytometry, HA uptake assay, ex vivo lung slices

    PMID:32736525

    Open questions at the time
    • Which NFAT family member is responsible not specified
    • In vivo significance for transplant-associated lymphatic dysfunction not tested
  17. 2024 Medium

    Osteopontin was identified as a non-HA ligand for LYVE-1 on tumor-associated macrophages, activating JNK/c-Jun to expand immunosuppressive LYVE-1+ macrophages, linking LYVE-1 to tumor immune evasion beyond its classical HA-binding role.

    Evidence In vitro JNK/c-Jun signaling assays, macrophage-specific LYVE-1 conditional KO, OPN neutralization, tumor growth models

    PMID:39643970

    Open questions at the time
    • OPN binding site on LYVE-1 not mapped
    • Whether OPN competes with HA for LYVE-1 binding unknown
    • Single-lab finding requiring independent validation
  18. 2025 High

    Crystal structures of LYVE-1–HA complexes from two species revealed a unique 'sliding' binding mode in which LYVE-1 grabs free HA chain-ends and winds them through a deep, water-lubricated cleft, explaining how immune cells retain their HA glycocalyx while sliding through lymphatic junctions—resolving the long-standing puzzle of low-tack adhesion.

    Evidence X-ray crystallography of murine and human LYVE-1–HA complexes, surface plasmon resonance, functional validation

    PMID:40113779

    Open questions at the time
    • Whether the sliding mechanism applies equally to all HA polymer sizes not tested
    • How sialylation inhibits binding at the structural level not shown in these structures
  19. 2025 High

    LYVE-1+ septal adipose tissue macrophages were found to instruct white adipocyte differentiation via TGFβ1, with their depletion redirecting adipocyte progenitors toward thermogenic beige fate and protecting against obesity, revealing a metabolic regulatory role for LYVE-1+ macrophages.

    Evidence Genetic depletion of LYVE-1+ macrophages, myeloid-specific TGFβ1 conditional KO, adipocyte lineage tracing, metabolic phenotyping

    PMID:40875853

    Open questions at the time
    • Whether LYVE-1 itself transduces signals in sATMs or serves only as a marker not distinguished
    • Relevance to human obesity not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the physiological signals that desialylate or cluster LYVE-1 above its activation threshold in vivo, the identity of cytoplasmic signaling adaptors, whether the sliding binding mode generalizes across all polymer contexts, and whether LYVE-1's roles on tissue-resident macrophages reflect receptor-mediated signaling or merely mark a macrophage subset.
  • Physiological desialylation trigger unknown
  • No cytoplasmic adaptor or signaling scaffold identified
  • Functional distinction between LYVE-1 as receptor vs. macrophage subset marker not resolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0038024 cargo receptor activity 5 GO:0098772 molecular function regulator activity 3
Localization
GO:0005886 plasma membrane 5
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 3 R-HSA-1474244 Extracellular matrix organization 1
Partners
ADAM17BSGFGF2PDGFBPDGFRBS1PR3SPP1VEGFA

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 LYVE-1 is a type I integral membrane glycoprotein with a single extracellular Link module that binds both soluble and immobilized hyaluronan (HA), functioning as the first characterized lymph-specific HA receptor on the luminal face of lymph vessel walls; it is 41% similar to CD44 but absent from blood vessels. Molecular cloning, recombinant protein HA-binding assays, immunolocalization (immunofluorescence and immunoelectron microscopy) The Journal of cell biology High 10037799
2001 Mouse LYVE-1 acts as an endocytic receptor for hyaluronan: it both binds and internalizes HA in transfected 293T fibroblasts in vitro, and is distributed equally on luminal and abluminal surfaces of lymphatic vessels in vivo. Transfection of 293T fibroblasts with murine LYVE-1 cDNA, HA internalization assay, immunoelectron microscopy of lymphatic vessels, LYVE-1/CD44 double-knockout analysis The Journal of biological chemistry High 11278811
2007 LYVE-1 surface expression is rapidly and reversibly lost from lymphatic endothelial cells after exposure to TNFα and TNFβ via internalization and lysosomal degradation, coupled with transcriptional shutdown; this internalization is largely HA-independent and occurs in vivo during allergen-induced skin inflammation. Primary lymphatic endothelial cell culture, cytokine treatment, flow cytometry, lysosomal inhibitor studies, ex vivo dermal explants, in vivo murine allergen model, adhesion-blocking mAb 3A The Journal of biological chemistry High 17884820
2008 LYVE-1 HA-binding activity is functionally silenced in lymphatic endothelial cells by cell-specific autoinhibitory terminal sialylation (via α2-3 or α2-6 linkage to O-glycans); neuraminidase treatment of the native ectodomain reactivates HA binding. Transfection into HEK 293T, Jurkat, CHO, and HeLa cells; mutagenesis of glycosylation sites; glycosylation-defective CHO cell lines; neuraminidase treatment; HA-binding assays The Journal of biological chemistry High 19033446
2009 The LYVE-1 HA-binding domain uses six key residues (Tyr-87, Ile-97, Arg-99, Asn-103, Lys-105, Lys-108) forming a compact, predominantly electrostatic binding surface; unlike CD44, the extended Link module of LYVE-1 requires artificial dimerization for efficient HA binding, and a third conserved disulfide is critical for binding. Truncation mutagenesis, site-directed mutagenesis, recombinant soluble ectodomain production, HA-binding assays, bioluminescent resonance energy transfer (BRET) for dimerization The Journal of biological chemistry High 19887450
2011 LYVE-1 (identical to CRSBP-1) interacts with PDGF-BB and VEGF-A via their CRS motifs; CRSBP-1 ligands induce disruption of VE-cadherin-mediated intercellular adhesion in lymphatic endothelial cells through tyrosine phosphorylation of the CRSBP-1–PDGFβR–β-catenin complex, dissociation of β-catenin and p120-catenin from VE-cadherin, VE-cadherin internalization, and opening of intercellular junctions both in vitro and in vivo. Co-immunoprecipitation, immunofluorescence microscopy, Transwell permeability assay, PDGFβR kinase inhibitor treatment, FITC-dextran injection in wild-type and Crsbp1-null mice Journal of cell science High 21444752
2012 FGF2 directly binds LYVE-1 with higher affinity than HA or PDGF-BB; glycosylation of LYVE-1 is required for FGF2 binding; soluble LYVE-1 and LYVE-1 knockdown impair FGF2 signaling and FGF2-induced lymphangiogenesis in vivo. AlphaScreen binding assay, surface-immobilization binding, solution-phase binding, CHO cell overexpression, siRNA knockdown in lymphatic endothelial cells, in vivo corneal lymphangiogenesis assay Blood High 23264596
2016 HA binding by native LYVE-1 in lymphatic endothelium is critically dependent on avidity: receptor self-association above a critical density threshold and/or HA multimerization (via streptavidin or TSG-6 complexes) is required; surface clustering with divalent LYVE-1 mAbs activates binding; endogenous macrophage-surface HA engages LYVE-1 to facilitate macrophage adhesion and transit across lymphatic endothelium. Primary lymphatic endothelial cell HA-binding assays, divalent antibody cross-linking, biotinylated HA multimerization with streptavidin or TSG-6, macrophage adhesion assays on lymphatic endothelium The Journal of biological chemistry High 26823460
2016 LYVE-1 forms obligate disulfide-linked homodimers via an unpaired cysteine (Cys-201) in the membrane-proximal domain; homodimerization yields ~15-fold higher HA-binding affinity and ~67-fold slower off-rate than monomers; non-dimerizing mutants fail to bind HA even at high density or after antibody cross-linking; small-angle X-ray scattering (SAXS) indicates the homodimer adopts an 'open scissors' conformation; the Cys-201 disulfide is redox-labile, acting as a potential redox switch. Site-directed mutagenesis of Cys-201, disulfide-linked dimer detection by non-reducing SDS-PAGE, SAXS structural analysis, HA-binding affinity and kinetics measurements, TCEP-HCl reduction assay, lymphatic endothelial cell transfection The Journal of biological chemistry High 27733683
2016 LYVE-1 ectodomain shedding is induced by VEGF-A via ERK and ADAM17 in lymphatic endothelial cells; wild-type but not uncleavable LYVE-1 promotes LEC migration in response to VEGF-A, implicating shedding in pathological lymphangiogenesis. Identification of cleavage site, generation of uncleavable LYVE-1 mutant, MEK inhibitor and ADAM17 inhibitor treatment, LEC migration assay, immunostaining in human psoriasis skin and VEGF-A transgenic mice The Journal of biological chemistry High 26966180
2017 Dendritic cells dock to the basolateral surface of lymphatic vessels and transit to the lumen through HA-mediated interactions with LYVE-1, forming transmigratory cup-like structures; targeted deletion of Lyve1, antibody blockade, or depletion of the DC HA coat delayed lymphatic DC trafficking and blunted CD8+ T cell priming in skin-draining lymph nodes. Intravital microscopy, Lyve1 gene-targeted deletion, anti-LYVE-1 antibody blockade, hyaluronidase treatment of DC HA coat, DC adoptive transfer, in vivo T cell priming assays Nature immunology High 28504698
2018 Arterial wall LYVE-1+ resident macrophages prevent arterial stiffness and collagen deposition by modulating collagen expression in smooth muscle cells via MMP-9-dependent proteolysis through engagement of LYVE-1 with the HA pericellular matrix of SMCs. Phenotyping and transcriptional profiling of aortic macrophages, targeted deletion of Csf1r, MMP-9 activity assays, co-culture of macrophages and SMCs, collagen quantification, arterial stiffness measurements Immunity High 30054204
2020 LYVE-1 lateral diffusion and HA-binding activity in primary lymphatic endothelial cells are regulated by the submembranous cortical actin network: actin disruption increases LYVE-1 diffusion and HA binding; LYVE-1 is transiently entrapped within actin corrals but unlike CD44 does not directly bind actin via cytoplasmic tail motifs. Super-resolution STED microscopy, fluorescence correlation spectroscopy, single-particle tracking, co-immunoprecipitation with actin, actin-disrupting drug treatments, HA-binding assays in primary LECs The Journal of biological chemistry High 32034091
2014 LMW-HA stimulation of lymphatic endothelial cells through LYVE-1 induces actin cytoskeleton rearrangement and rapid tyrosine phosphorylation of PKCα/βII and ERK1/2; neutralizing anti-LYVE-1 antibodies block these effects as well as LEC proliferation, migration, and tube formation. Primary LEC culture, anti-LYVE-1 neutralizing antibody, western blotting for phospho-PKC and phospho-ERK, actin immunofluorescence, proliferation and migration assays, tube formation assay PloS one Medium 24667755
2015 LMW-HA increases colocalization of LYVE-1 and S1P receptor S1P3 at the LEC surface; silencing either LYVE-1 or S1P3 inhibits LMW-HA-induced tube formation and blocks Src and ERK1/2 phosphorylation, indicating cooperative signaling between LYVE-1 and S1P3 in LMW-HA-mediated lymphangiogenesis. Immunofluorescence colocalization, co-immunoprecipitation, siRNA knockdown of LYVE-1 or S1P3, phospho-Src and phospho-ERK western blot, tube formation assay Experimental cell research Medium 26116468
2006 LYVE-1 knockout mice display normal lymphatic vessel ultrastructure and function, normal hyaluronan levels in tissue and blood, normal dendritic cell trafficking, normal skin inflammation resolution, and normal tumor growth, indicating LYVE-1 is not obligatory for these processes under normal conditions. Targeted gene replacement with beta-galactosidase reporter, immunoelectron microscopy, HA quantification in blood and tissue, DC trafficking assays, oxazolone inflammation model, tumor transplant models Molecular and cellular biology High 17101772
2009 LYVE-1/CD44 double-knockout mice show increased edema formation in a carrageenan-induced paw inflammation model compared to wild-type, but not to single knockouts, suggesting LYVE-1 and CD44 have overlapping roles in inflammation, though neither is individually required for lymphatic formation or function. Generation of LYVE-1/CD44 double KO mice, histology, intravital microscopy, carrageenan-induced edema model Journal of cellular physiology Medium 19170073
2020 FK506 (tacrolimus) downregulates LYVE-1 mRNA and protein in lymphatic endothelial cells through an NFAT-dependent transcriptional mechanism (identified via luciferase reporter assay with NFAT binding site on LYVE-1 promoter), resulting in decreased HA uptake; this effect was confirmed ex vivo in precision-cut lung slices. LEC culture, luciferase reporter assay with NFAT binding site mutagenesis, western blot, flow cytometry, HA uptake assay, ex vivo lung slice treatment Molecular medicine Medium 32736525
2017 Small HA (sHA) oligosaccharides promote LEC proliferation and lymphangiogenesis in a LYVE-1-dependent manner (using sialylated LYVE-1, not CD44 or TLR-4); higher sHA concentrations induce TGFβ in LECs to counter-regulate this proliferation; effects confirmed with LYVE-1 knockout mice and blocking antibodies. Primary LEC proliferation assays, ex vivo lymphangiogenesis assay, in vivo intradermal injection, LYVE-1 KO mice, blocking antibodies, TGFβ measurement Journal of molecular medicine Medium 29282520
2024 OPN (osteopontin) acts as a ligand for LYVE-1 on tissue-resident macrophages (TRM-TAMs); OPN/LYVE-1 signaling activates the JNK/c-Jun pathway, promoting proliferation of immunosuppressive LYVE-1+ TRM-TAMs; IL-17A stimulates tumor cell CEBPβ to produce OPN; LYVE-1 deletion in macrophages inhibited TRM-TAM expansion and enhanced anti-tumor responses. In vitro signaling assays (JNK/c-Jun phosphorylation), macrophage-specific LYVE-1 conditional KO, OPN neutralization, IL-17A neutralization, tumor growth models, flow cytometry Cell reports Medium 39643970
2025 Crystal structures of murine and human LYVE-1 bound to hyaluronan reveal a highly unusual 'sliding' mode of ligand interaction (unlike the conventional 'sticking' mode of CD44): LYVE-1 grabs free HA chain-ends and winds them through conformational rearrangements in a deep binding cleft lubricated by structured waters, providing a low-tack adhesive interaction that allows migrating immune cells to slide through endothelial junctions while retaining their HA glycocalyx. X-ray crystallography of murine and human LYVE-1–HA complexes, surface plasmon resonance/binding mechanics, functional validation Nature communications High 40113779
2025 Septal adipose tissue macrophages (sATMs) marked by LYVE-1 and CD209b reside in close proximity to adipocyte stem cells (ASCs) in the WAT septum; sATMs instruct ASC differentiation into white adipocytes through TGFβ1; depletion of sATMs or myeloid-specific loss of TGFβ1 redirects ASC fate toward thermogenic (beige) adipocytes and protects against diet-induced obesity. Genetic mouse model of LYVE-1+ macrophage depletion, TGFβ1 conditional KO in tissue-resident macrophages, adipocyte lineage tracing, co-culture of sATMs and ASCs, metabolic phenotyping Science High 40875853
2011 LYVE-1 expressed on primary effusion lymphoma (PEL) cells interacts and colocalizes with emmprin (CD147) and BCRP/ABCG2 at the cell surface; RNA interference targeting of LYVE-1 enhances chemotherapy-induced apoptosis, and disruption of HA-receptor interactions with small HA oligosaccharides reduces emmprin and BCRP expression, sensitizing PEL cells to chemotherapy. Co-immunoprecipitation, immunofluorescence colocalization, siRNA knockdown of LYVE-1, apoptosis assay, small HA oligosaccharide treatment Leukemia Medium 21660043

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 LYVE-1, a new homologue of the CD44 glycoprotein, is a lymph-specific receptor for hyaluronan. The Journal of cell biology 1308 10037799
2001 Mouse LYVE-1 is an endocytic receptor for hyaluronan in lymphatic endothelium. The Journal of biological chemistry 395 11278811
2001 LYVE-1 is not restricted to the lymph vessels: expression in normal liver blood sinusoids and down-regulation in human liver cancer and cirrhosis. Cancer research 350 11719431
2001 LYVE-1, the lymphatic system and tumor lymphangiogenesis. Trends in immunology 284 11377291
2018 Hyaluronan Receptor LYVE-1-Expressing Macrophages Maintain Arterial Tone through Hyaluronan-Mediated Regulation of Smooth Muscle Cell Collagen. Immunity 267 30054204
2007 Angiogenic role of LYVE-1-positive macrophages in adipose tissue. Circulation research 240 17272806
2006 Lymphatic endothelium-specific hyaluronan receptor LYVE-1 is expressed by stabilin-1+, F4/80+, CD11b+ macrophages in malignant tumours and wound healing tissue in vivo and in bone marrow cultures in vitro: implications for the assessment of lymphangiogenesis. The Journal of pathology 228 16482496
2002 Lymphatic vessels in vascularized human corneas: immunohistochemical investigation using LYVE-1 and podoplanin. Investigative ophthalmology & visual science 198 12091407
2005 Angiopoietin-1 promotes LYVE-1-positive lymphatic vessel formation. Blood 197 15705793
2004 Biology of the lymphatic marker LYVE-1 and applications in research into lymphatic trafficking and lymphangiogenesis. APMIS : acta pathologica, microbiologica, et immunologica Scandinavica 177 15563314
2012 lyve1 expression reveals novel lymphatic vessels and new mechanisms for lymphatic vessel development in zebrafish. Development (Cambridge, England) 172 22627281
2003 The lymphatics revisited: new perspectives from the hyaluronan receptor LYVE-1. Trends in cardiovascular medicine 171 12554094
2006 Normal lymphatic development and function in mice deficient for the lymphatic hyaluronan receptor LYVE-1. Molecular and cellular biology 166 17101772
2017 Dendritic cells enter lymph vessels by hyaluronan-mediated docking to the endothelial receptor LYVE-1. Nature immunology 150 28504698
2004 High LYVE-1-positive lymphatic vessel numbers are associated with poor outcome in breast cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 150 15534085
2007 Inflammation-induced uptake and degradation of the lymphatic endothelial hyaluronan receptor LYVE-1. The Journal of biological chemistry 122 17884820
2018 Hyaluronan in the lymphatics: The key role of the hyaluronan receptor LYVE-1 in leucocyte trafficking. Matrix biology : journal of the International Society for Matrix Biology 116 29425695
2007 LYVE-1-positive macrophages are present in normal murine eyes. Investigative ophthalmology & visual science 105 17460275
2008 Expression of the hyaluronan receptor LYVE-1 is not restricted to the lymphatic vasculature; LYVE-1 is also expressed on embryonic blood vessels. Developmental dynamics : an official publication of the American Association of Anatomists 104 18570254
2016 Binding of Hyaluronan to the Native Lymphatic Vessel Endothelial Receptor LYVE-1 Is Critically Dependent on Receptor Clustering and Hyaluronan Organization. The Journal of biological chemistry 96 26823460
2008 The normal human choroid is endowed with a significant number of lymphatic vessel endothelial hyaluronate receptor 1 (LYVE-1)-positive macrophages. Investigative ophthalmology & visual science 87 18689706
2014 Low molecular weight hyaluronan induces lymphangiogenesis through LYVE-1-mediated signaling pathways. PloS one 82 24667755
2016 LYVE1 Marks the Divergence of Yolk Sac Definitive Hemogenic Endothelium from the Primitive Erythroid Lineage. Cell reports 63 27880904
2012 Evidence for the interaction of fibroblast growth factor-2 with the lymphatic endothelial cell marker LYVE-1. Blood 62 23264596
2022 Deciphering the heterogeneity of the Lyve1+ perivascular macrophages in the mouse brain. Nature communications 59 36450771
2013 Conditional ablation of LYVE-1+ cells unveils defensive roles of lymphatic vessels in intestine and lymph nodes. Blood 59 23836558
2008 DC-sign+ CD163+ macrophages expressing hyaluronan receptor LYVE-1 are located within chorion villi of the placenta. Placenta 59 18078989
2019 Long noncoding RNA ANRIL regulates endothelial cell activities associated with coronary artery disease by up-regulating CLIP1, EZR, and LYVE1 genes. The Journal of biological chemistry 58 30655286
2004 Lymph and blood vessel architecture in benign and malignant prostatic tissue: lack of lymphangiogenesis in prostate carcinoma assessed with novel lymphatic marker lymphatic vessel endothelial hyaluronan receptor (LYVE-1). The Journal of urology 58 15201747
2011 Cooperative roles for emmprin and LYVE-1 in the regulation of chemoresistance for primary effusion lymphoma. Leukemia 53 21660043
2005 Novel expression and characterization of lymphatic vessel endothelial hyaluronate receptor 1 (LYVE-1) by conjunctival cells. Investigative ophthalmology & visual science 52 16303945
2021 LYVE1+ macrophages of murine peritoneal mesothelium promote omentum-independent ovarian tumor growth. The Journal of experimental medicine 51 34714329
2008 A mechanism of sialylation functionally silences the hyaluronan receptor LYVE-1 in lymphatic endothelium. The Journal of biological chemistry 51 19033446
2004 Immunohistochemical detection of human small lymphatic vessels under normal and pathological conditions using the LYVE-1 antibody. Virchows Archiv : an international journal of pathology 51 14722766
2010 Expression of lymphatic endothelium-specific hyaluronan receptor LYVE-1 in the developing mouse kidney. Cell and tissue research 48 21181199
2009 Distinctive properties of the hyaluronan-binding domain in the lymphatic endothelial receptor Lyve-1 and their implications for receptor function. The Journal of biological chemistry 47 19887450
2005 The use of LYVE-1 antibody for detecting lymphatic involvement in patients with malignant melanoma of known sentinel node status. Journal of clinical pathology 46 15976338
2009 Expression of LYVE-1 in sinusoidal endothelium is reduced in chronically inflamed human livers. Journal of gastroenterology 44 19908110
2008 Fluorescent LYVE-1 antibody to image dynamically lymphatic trafficking of cancer cells in vivo. The Journal of surgical research 44 18599080
2023 LYVE-1+ macrophages form a collaborative CCR5-dependent perivascular niche that influences chemotherapy responses in murine breast cancer. Developmental cell 40 37442140
2021 Nectin-4 promotes lymphangiogenesis and lymphatic metastasis in breast cancer by regulating CXCR4-LYVE-1 axis. Vascular pharmacology 39 33945869
2009 Lack of lymphatic vessel phenotype in LYVE-1/CD44 double knockout mice. Journal of cellular physiology 35 19170073
2016 Ectodomain Shedding of Lymphatic Vessel Endothelial Hyaluronan Receptor 1 (LYVE-1) Is Induced by Vascular Endothelial Growth Factor A (VEGF-A). The Journal of biological chemistry 34 26966180
2011 CRSBP-1/LYVE-1 ligands disrupt lymphatic intercellular adhesion by inducing tyrosine phosphorylation and internalization of VE-cadherin. Journal of cell science 34 21444752
2006 Expression of lymphatic vascular endothelial hyaluronan receptor-1 (LYVE-1) in the human placenta. Lymphatic research and biology 34 16569201
2005 A quantitative analysis of lymphatic vessels in human breast cancer, based on LYVE-1 immunoreactivity. British journal of cancer 33 16251871
2015 The cooperative role of S1P3 with LYVE-1 in LMW-HA-induced lymphangiogenesis. Experimental cell research 31 26116468
2014 Enrichment of lymphatic vessel endothelial hyaluronan receptor 1 (LYVE1)-positive macrophages around blood vessels in the normal human sclera. Investigative ophthalmology & visual science 31 24436193
2009 Lymphatic vascularisation and involvement of Lyve-1+ macrophages in the human onchocerca nodule. PloS one 31 20011036
2022 Kinetics of LYVE-1-positive M2-like macrophages in developing and repairing dental pulp in vivo and their pro-angiogenic activity in vitro. Scientific reports 30 35338195
2007 Significance of lymphatic invasion on regional lymph node metastasis in early gastric cancer using LYVE-1 immunohistochemical analysis. American journal of clinical pathology 30 17145628
2005 LYVE-1 expression on high endothelial venules (HEVs) of lymph nodes. Lymphology 30 16353487
2022 Single-Cell RNA-Seq Reveals a Crosstalk between Hyaluronan Receptor LYVE-1-Expressing Macrophages and Vascular Smooth Muscle Cells. Cells 29 35159221
2017 The shedded ectodomain of Lyve-1 expressed on M2-like tumor-associated macrophages inhibits melanoma cell proliferation. Oncotarget 29 29262593
2007 Basement membrane protein distribution in LYVE-1-immunoreactive lymphatic vessels of normal tissues and ovarian carcinomas. Cell and tissue research 29 17265066
2007 Investigation of intratumoural and peritumoural lymphatics expressed by podoplanin and LYVE-1 in the hybridoma-induced tumours. International journal of experimental pathology 26 17696907
2020 Identification of Lyve-1 positive macrophages as resident cells in meninges of rats. The Journal of comparative neurology 25 32003471
2017 TGFβ counteracts LYVE-1-mediated induction of lymphangiogenesis by small hyaluronan oligosaccharides. Journal of molecular medicine (Berlin, Germany) 25 29282520
2016 Homodimerization of the Lymph Vessel Endothelial Receptor LYVE-1 through a Redox-labile Disulfide Is Critical for Hyaluronan Binding in Lymphatic Endothelium. The Journal of biological chemistry 25 27733683
2016 The selective distribution of LYVE-1-expressing endothelial cells and reticular cells in the reticulo-endothelial system (RES). Biomedical research (Tokyo, Japan) 24 27356606
2006 Expression and quantification of LYVE-1 in human colorectal cancer. Clinical and experimental medicine 23 16820993
2013 The interaction between LYVE-1 with hyaluronan on the cell surface may play a role in the diversity of adhesion to cancer cells. PloS one 22 23717428
2013 Mouse lymphatic endothelial cell targeted probes: anti-LYVE-1 antibody-based magnetic nanoparticles. International journal of nanomedicine 21 23818783
2011 Induction of LYVE-1/stabilin-2-positive liver sinusoidal endothelial-like cells from embryoid bodies by modulation of adrenomedullin-RAMP2 signaling. Peptides 20 21782867
2011 Discontinuous LYVE-1 expression in corneal limbal lymphatics: dual function as microvalves and immunological hot spots. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 20 22090317
2011 Proinflammatory signals and the loss of lymphatic vessel hyaluronan receptor-1 (LYVE-1) in the early pathogenesis of laminin alpha2-deficient skeletal muscle. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 19 20876525
2024 MRC1 and LYVE1 expressing macrophages in vascular beds of GNAQ p.R183Q driven capillary malformations in Sturge Weber syndrome. Acta neuropathologica communications 18 38532508
2010 Novel discovery of LYVE-1 expression in the hyaloid vascular system. Investigative ophthalmology & visual science 18 20688736
2020 The cortical actin network regulates avidity-dependent binding of hyaluronan by the lymphatic vessel endothelial receptor LYVE-1. The Journal of biological chemistry 17 32034091
2022 Lyve-1 deficiency enhances the hepatic immune microenvironment entailing altered susceptibility to melanoma liver metastasis. Cancer cell international 16 36496412
2014 Three types of macrophagic cells in the mesentery of mice with special reference to LYVE-1-immunoreactive cells. Biomedical research (Tokyo, Japan) 16 24573200
2017 The effect of neoadjuvant chemotherapy on the correlation of tumor-associated macrophages with CD31 and LYVE-1. Immunobiology 15 29459011
2006 Infantile hemangioma is a proliferation of LYVE-1-negative blood endothelial cells without lymphatic competence. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 15 16424896
2019 Elevated lymphatic vessel density measured by Lyve-1 expression in areas of replacement fibrosis in the ventricular septum of patients with hypertrophic obstructive cardiomyopathy (HOCM). Heart and vessels 14 31250132
2008 Distribution and organization of lymphatic vessels in the mouse gingiva: An immunohistochemical study with LYVE-1. Archives of oral biology 14 18316062
2006 Lymphatic vascular endothelial hyaluronan receptor (LYVE)-1- and CCL21-positive lymphatic compartments in the diabetic thymus. Anatomical science international 14 17176958
2025 Septal LYVE1+ macrophages control adipocyte stem cell adipogenic potential. Science (New York, N.Y.) 13 40875853
2011 Lymph vessel density in seminomatous testicular cancer assessed with the specific lymphatic endothelium cell markers D2-40 and LYVE-1: correlation with pathologic parameters and clinical outcome. Urologic oncology 12 21974896
2025 Structure and unusual binding mechanism of the hyaluronan receptor LYVE-1 mediating leucocyte entry to lymphatics. Nature communications 11 40113779
2025 MHCIIhiLYVE1loCCR2hi Interstitial Macrophages Promote Medial Fibrosis in Pulmonary Arterioles and Contribute to Pulmonary Hypertension. Circulation research 11 40357547
2024 IL-17A/CEBPβ/OPN/LYVE-1 axis inhibits anti-tumor immunity by promoting tumor-associated tissue-resident macrophages. Cell reports 11 39643970
2021 Adventitial recruitment of Lyve-1- macrophages drives aortic aneurysm in an angiotensin-2-based murine model. Clinical science (London, England : 1979) 11 33978148
2008 The lymph vessel network in mouse skin visualised with antibodies against the hyaluronan receptor LYVE-1. Immunobiology 11 18926287
2024 LYVE-1-expressing Macrophages Modulate the Hyaluronan-containing Extracellular Matrix in the Mammary Stroma and Contribute to Mammary Tumor Growth. Cancer research communications 10 38717149
2013 Characterization of cells expressing lymphatic marker LYVE-1 in macaque large intestine during simian immunodeficiency virus infection identifies a large population of nonvascular LYVE-1(+)/DC-SIGN(+) cells. Lymphatic research and biology 9 23531182
2005 Lymphatic vessel density in vocal cord carcinomas assessed with LYVE-1 receptor expression. Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology 9 16229916
2016 Effects of Melatonin, Aluminum Oxide, and Polymethylsiloxane Complex on the Expression of LYVE-1 in the Liver of Mice with Obesity and Type 2 Diabetes Mellitus. Bulletin of experimental biology and medicine 8 27909960
2011 LYVE-1 enhances the adhesion of HS-578T cells to COS-7 cells via hyaluronan. Clinical and investigative medicine. Medecine clinique et experimentale 8 21291635
2011 Absence of Nkx2-3 homeodomain transcription factor induces the formation of LYVE-1-positive endothelial cysts without lymphatic commitment in the spleen. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 8 21705651
2023 Prostaglandin E2 Boosts the Hyaluronan-Mediated Increase in Inflammatory Response to Lipopolysaccharide by Enhancing Lyve1 Expression. Biology 6 37998039
2021 Pilot study supporting the existence of novel lymphatic channels within the canine anterior uveal tract using Lyve-1 and CD31. Veterinary ophthalmology 6 33977630
2020 FK506 induces lung lymphatic endothelial cell senescence and downregulates LYVE-1 expression, with associated decreased hyaluronan uptake. Molecular medicine (Cambridge, Mass.) 6 32736525
2018 A novel role of HIF-1α/PROX-1/LYVE-1 axis on tissue regeneration after renal ischaemia/reperfusion in mice. Archives of physiology and biochemistry 6 29633855
2016 Thymocytes in Lyve1-CRE/S1pr1f/f Mice Accumulate in the Thymus due to Cell-Intrinsic Loss of Sphingosine-1-Phosphate Receptor Expression. Frontiers in immunology 6 27877175
2016 LYVE1 and PROX1 in the reconstruction of hepatic sinusoids after partial hepatectomy in mice. Folia morphologica 6 28026853
2011 [Expression of LYVE-1 and Prox-1 in non-small cell lung cancer and the relationship with lymph node metastasis]. Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition 6 21500548
2025 Spatial mapping of rheumatoid arthritis synovial niches reveals a LYVE1+ macrophage network associated with response to therapy. Annals of the rheumatic diseases 5 40849271
2024 Novel erectile analyses revealed augmentable penile Lyve-1, the lymphatic marker, expression. Reproductive medicine and biology 5 38566911
2023 Single-cell RNA-Seq reveals CVI-mAb-induced Lyve1+ M2-like macrophages reduce atherosclerotic plaque area in Apoe-/- mice. International immunopharmacology 5 36736225
2022 Thiocyanate Reduces Motor Impairment in the hMPO-A53T PD Mouse Model While Reducing MPO-Oxidation of Alpha Synuclein in Enlarged LYVE1/AQP4 Positive Periventricular Glymphatic Vessels. Antioxidants (Basel, Switzerland) 5 36552550