Affinage

Showing ACKR1 — DARC is a alias.

ACKR1

Atypical chemokine receptor 1 · UniProt Q16570

Length
336 aa
Mass
35.6 kDa
Annotated
2026-06-09
100 papers in source corpus 29 papers cited in narrative 29 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ACKR1 (DARC/Duffy) is an atypical seven-transmembrane chemokine receptor that binds pro-inflammatory CXC and CC chemokines without coupling to G-protein signaling, instead acting as a high-capacity chemokine handling system that shapes inflammation (PMID:10961863, PMID:13679391, PMID:37153544). On erythrocytes it functions as a chemokine sink/reservoir: it internalizes and sequesters ligands such as CXCL1, CCL2, CCL5, and CXCL8 from plasma, and its loss elevates circulating and tissue chemokine levels and exaggerates inflammatory leukocyte infiltration (PMID:7699323, PMID:10961863, PMID:19499525). Release of reservoir chemokines is triggered by clotting and heparan sulfate, and the common rs12075 (Asp42Gly) variant is a major determinant of erythrocyte chemokine-binding capacity (PMID:20040767). On post-capillary venular endothelium, where it concentrates at cell-cell junctions, ACKR1 mediates abluminal-to-luminal transcytosis of chemokines and presents them as junctional depots—notably neutrophil-derived CXCL2—to direct unidirectional transendothelial neutrophil and T-cell migration (PMID:24625696, PMID:28526034, PMID:30446388, PMID:34524684). Ligand recognition depends on a sulphated N-terminal ectodomain in which tyrosine 30 supports CXCL8 binding and tyrosine 41 supports binding of other chemokines (PMID:15720550). This same ectodomain is the obligate erythrocyte receptor for Plasmodium vivax/knowlesi invasion: binding of the parasite Duffy-binding protein RII drives its dimerization, and the sulphated tyrosine 41 docks into a charged pocket on PvDBP-RII, with conformational exposure of this site on immature reticulocytes explaining parasite tropism (PMID:15720550, PMID:21743458, PMID:24415938, PMID:37336887, PMID:28754683). The N-terminal ectodomain is also the receptor for the Staphylococcus aureus leukocidins LukED and HlgAB, mediating erythrocyte lysis, endothelial injury, and toxin lethality in vivo (PMID:26320997, PMID:30799265). Independently, endothelial and bone-marrow-macrophage ACKR1 binds the metastasis suppressor KAI1/CD82, stabilizing its surface expression to induce tumor-cell senescence and to enforce TGF-β1/Smad3-mediated quiescence of long-term hematopoietic stem cells (PMID:16862154, PMID:26996598).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1995 High

    Established that erythrocyte DARC actively internalizes chemokine ligands and that erythroid and endothelial DARC are independently regulated, defining DARC as a chemokine-handling receptor rather than a passive binder.

    Evidence Radiolabeled ligand internalization in transfectants plus IHC and biochemistry in Duffy-negative tissues

    PMID:7699323

    Open questions at the time
    • Did not establish whether internalized chemokine is degraded or recycled
    • No demonstration of a signaling-independent mechanism
  2. 2000 High

    Knockout mice showed that DARC functions as a chemokine sink modulating inflammation intensity and neutrophil migration, moving the receptor from in vitro binder to in vivo immunoregulator.

    Evidence Two independent Darc-null mouse lines challenged with LPS/thioglycolate, with erythrocyte chemokine-binding assays

    PMID:10757794 PMID:10961863

    Open questions at the time
    • Could not separate erythroid from endothelial contributions
    • Receptor appeared largely redundant for development and most immune parameters
  3. 2003 High

    Demonstrated chemokine selectivity (pro-inflammatory but not lymphoid) and that DARC binding silences chemokine activity without triggering Ca2+ flux, defining its non-signaling decoy/scavenger character.

    Evidence Competitive binding of 20 chemokines, Ca2+ flux assay in CCR2B cells, KO mice

    PMID:13679391

    Open questions at the time
    • Did not resolve the fate of bound chemokine on endothelium
    • Mechanism of presentation versus sequestration unresolved
  4. 2005 High

    Mapped the structural basis of ligand recognition to sulphated tyrosines, showing Tyr41 and Tyr30 differentially govern chemokine and parasite-protein binding via the N-terminal ectodomain.

    Evidence Tyr-to-Phe mutagenesis, cell-based binding, and soluble peptide inhibition of PvDBP/PkDaBP

    PMID:15720550

    Open questions at the time
    • No atomic structure of the sulphated interface at this stage
    • Did not address conformational regulation of the ectodomain
  5. 2006 High

    Linked DARC to tumor biology in two ways: as a direct KAI1/CD82 binding partner inducing tumor-cell senescence, and as an erythrocyte clearer of angiogenic chemokines limiting tumor vascularization.

    Evidence Yeast two-hybrid plus KO metastasis model; erythrocyte chemokine clearance assays and DARC-KO prostate tumor model

    PMID:16394268 PMID:16862154

    Open questions at the time
    • Did not define the structural KAI1-binding interface on DARC
    • Downstream senescence pathway only partially mapped (TBX2, p21)
  6. 2007 Medium

    Extended the senescence/anti-angiogenic role to endothelial DARC and identified a negative role in bone density via osteoclast regulation, broadening the physiological reach of chemokine handling.

    Evidence Matrigel angiogenesis assays with anti-Fy6 blockade and KO mice; QTL mapping and in vitro osteoclast assays with chemokine affinity comparisons

    PMID:17416748 PMID:17955335

    Open questions at the time
    • Single-lab studies
    • Causal chemokine intermediaries in osteoclast and angiogenesis phenotypes not fully defined
  7. 2009 High

    Bone-marrow chimeras separated erythrocyte from endothelial DARC, showing erythrocyte DARC sets plasma chemokine levels while endothelial DARC governs leukocyte adhesion and transmigration.

    Evidence Darc-/- mice with bone marrow chimeras in LPS acute lung injury, ELISA and flow cytometry

    PMID:19499525

    Open questions at the time
    • Molecular mechanism of endothelial chemokine presentation not yet defined
    • Did not address junctional localization
  8. 2010 Medium

    Connected reservoir handling to genetics and to cell-adhesion modulation, with rs12075 controlling erythrocyte chemokine binding and DARC tuning integrin activation on reticulocytes.

    Evidence GWAS (n=9598) with ex vivo chemokine-release assays; static adhesion and conformation-sensitive integrin assays on sickle reticulocytes

    PMID:20040767 PMID:21088296

    Open questions at the time
    • Release mechanism inferred from ex vivo assays, not reconstituted
    • Integrin modulation shown for clustering rather than affinity change in a single system
  9. 2014 High

    Defined the structural mechanism of parasite engagement (PvDBP-RII dimerization-coupled binding with the ectodomain forming an amphipathic helix) and established endothelial DARC as the transcytosis conduit required for CNS inflammation.

    Evidence X-ray crystallography, NMR, ITC and RBC binding mutagenesis for PvDBP; BBB transcytosis model and EAE chimeras for endothelial function

    PMID:21743458 PMID:24415938 PMID:24625696

    Open questions at the time
    • Stoichiometry of physiological invasion complexes on intact erythrocytes not directly observed
    • Transcytosis machinery cooperating with DARC not identified
  10. 2015 High

    Identified DARC as the erythrocyte receptor for S. aureus leukocidins LukED and HlgAB, with expression level dictating lysis susceptibility and supporting bacterial hemoglobin acquisition.

    Evidence Natural human polymorphism analysis, DARC overexpression sufficiency, direct binding and hemolysis assays

    PMID:26320997

    Open questions at the time
    • Did not resolve distinct toxin-binding regions structurally
    • In vivo relevance addressed only later
  11. 2016 High

    Showed bone-marrow macrophage DARC binds and stabilizes CD82 on hematopoietic stem cells to enforce TGF-β1/Smad3 quiescence, generalizing the DARC-KAI1 senescence axis to stem-cell maintenance.

    Evidence Cd82-/- mice, macrophage ablation, flow cytometry and TGF-β1/Smad3 signaling and cell-cycle assays

    PMID:26996598

    Open questions at the time
    • Direct DARC-CD82 binding interface not structurally defined
    • Whether chemokine binding influences this interaction unknown
  12. 2017 Medium

    Pinpointed the endothelial niche (post-capillary venules, junction-concentrated) where leukocyte adhesion occurs, and showed conformational exposure of the DBP-binding site on immature reticulocytes explains P. vivax tropism.

    Evidence Purpose-built anti-DARC monoclonal antibodies, tissue immunostaining and intravital microscopy; reticulocyte maturation flow cytometry with DBP binding; pancreatic cancer DARC knockdown CXCR2/STAT3 assays

    PMID:28214673 PMID:28526034 PMID:28754683

    Open questions at the time
    • Reticulocyte conformational change inferred without direct structure
    • CXCR2/STAT3 suppression shown in single cancer model
  13. 2018 High

    Resolved how endothelial ACKR1 directs migration: it presents neutrophil-derived CXCL2 as a junctional depot enabling unidirectional luminal-to-abluminal neutrophil transmigration.

    Evidence Confocal intravital microscopy of cytokine-stimulated cremaster muscle in ACKR1-KO mice

    PMID:30446388

    Open questions at the time
    • Molecular basis of directionality not fully defined
    • Generalizability to other chemokines/leukocytes addressed separately
  14. 2019 High

    Established endothelial DARC as the critical in vivo target of S. aureus leukocidins for lethality, and refined erythroid DARC's conformation-dependent handling of CXCL12.

    Evidence Endothelial conditional DARC-KO mice with toxin and bloodstream infection models; CXCL12/SDF-1 binding assays across erythroid maturation with IL-8/antibody induction

    PMID:30799265 PMID:31700087

    Open questions at the time
    • CXCL12 binding consequences for trafficking not established
    • Conformational switch mechanism inferred indirectly
  15. 2021 Medium

    Showed endothelial ACKR1 biases T-cell diapedesis toward the transcellular route at the blood-brain barrier, extending its junctional migratory role beyond neutrophils.

    Evidence RNA-seq, ACKR1 KO in primary brain microvascular endothelial cells under flow, T-cell diapedesis assay

    PMID:34524684

    Open questions at the time
    • Single in vitro system
    • Mechanistic link between ACKR1 and transcellular pathway selection unresolved
  16. 2023 High

    Provided atomic detail of the sulphated interaction, showing DARC Tyr41-sulphate docks into a charged PvDBP-RII pocket, and defining a growth-inhibitory vaccine epitope.

    Evidence Crystal structure of PvDBP-RII with sulphated DARC peptide, MD simulations, affinity measurements and parasite growth inhibition

    PMID:37336887

    Open questions at the time
    • Full receptor context on intact reticulocytes not captured
    • Translation to broadly protective vaccine not yet achieved
  17. 2024 Medium

    Expanded endothelial ACKR1's pathological roles—FOLR2+ macrophage recruitment in tendon repair and an ACKR1/NF-κB/SPP1 axis driving aortic dissection—and identified anti-ACKR1 autoantibodies mediating endothelial ADCC after COVID-19.

    Evidence Bone marrow chimeras with scRNA-seq/proteomics (tendon); gain/loss-of-function ECs with NF-κB analysis and TAAD mouse model; patient IgG ADCC assays with blocking peptide rescue

    PMID:38714649 PMID:38740432 PMID:39692014

    Open questions at the time
    • Each finding from a single lab/model
    • Direct versus indirect role of ACKR1 in NF-κB/SPP1 signaling not fully separated
    • Autoantibody clinical relevance not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • How ACKR1's non-signaling chemokine binding, transcytosis, junctional presentation, and protein-protein partnerships (KAI1/CD82) are coordinated at the molecular level—and which trafficking machinery executes transcytosis and EV secretion—remains undefined.
  • No structural model of the chemokine-bound endothelial receptor at junctions
  • Transcytosis and EV-secretion machinery unidentified
  • Structural basis of the DARC-CD82 interaction unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0001618 virus receptor activity 6 GO:0140313 molecular sequestering activity 4 GO:0098772 molecular function regulator activity 3 GO:0048018 receptor ligand activity 2
Localization
GO:0005886 plasma membrane 3 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-1643685 Disease 5 R-HSA-168256 Immune System 4 R-HSA-1500931 Cell-Cell communication 3 R-HSA-162582 Signal Transduction 3
Partners
CCL2CD82CXCL12CXCL2CXCL8

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 DARC (ACKR1) expressed on erythrocytes internalizes radiolabeled chemokine ligands upon transfection, whereas endothelial DARC expression is maintained in Duffy-negative individuals who lack erythrocyte DARC, indicating tissue-specific regulatory mechanisms for DARC expression. Radiolabeled ligand internalization assay, immunohistochemistry, biochemical and molecular biological analysis of tissues from Duffy-negative individuals The Journal of experimental medicine High 7699323
2000 DARC knockout mice lacking both erythroid and endothelial DARC show exaggerated inflammatory infiltrates in lung and liver following LPS challenge, and erythrocytes from null mice lack CXC and CC chemokine-binding activity, demonstrating DARC functions as a chemokine sink that modulates inflammation intensity. Targeted gene disruption (knockout mice), LPS challenge model, hematological analysis, chemokine binding assay on erythrocytes Blood High 10961863
2000 Deletion of murine Dfy (DARC ortholog) reduces neutrophil migration into the peritoneal cavity and intestines/lungs following LPS/thioglycolate challenge, establishing a role for DARC in the neutrophil migratory process, though the receptor appears functionally redundant for most developmental and immune parameters. Targeted gene deletion (Dfy−/− mice), peritoneal inflammation models (LPS and thioglycolate), histological analysis of neutrophil recruitment Molecular and cellular biology High 10757794
2003 DARC expressed on high endothelial venules (HEV) selectively binds pro-inflammatory chemokines (CXCL1, CXCL5, CCL2, CCL5, CCL7) but not lymphoid chemokines (CCL21, CCL19, CXCL12, CXCL13); DARC-bound CCL2 failed to induce Ca2+ elevation in CCR2B-expressing cells, indicating DARC down-regulates pro-inflammatory chemokine activity upon binding without G-protein signaling. Competitive binding experiments with 20 chemokines, cytosolic Ca2+ elevation assay, targeted gene disruption, lymphocyte trafficking assay International immunology High 13679391
2005 DARC tyrosines 30 and 41 are sulphated; sulphated tyrosine 41 is essential for binding of P. vivax Duffy binding protein (PvDBP) and P. knowlesi (PkDaBP), and participates in association with chemokines MCP-1, RANTES, and MGSA but not IL-8; sulphated tyrosine 30 is required for IL-8 binding; a soluble sulphated N-terminal DARC domain blocks PvDBP/PkDaBP binding to RBCs with IC50 ~5 nM. Tyrosine-to-phenylalanine mutagenesis, cell-based binding assays, soluble peptide inhibition assay Molecular microbiology High 15720550
2006 DARC on vascular endothelium interacts directly with KAI1 (CD82) on tumor cells; this interaction leads to inhibition of tumor cell proliferation, induction of senescence, and modulation of TBX2 and p21 expression; DARC knockout mice showed significantly compromised KAI1-mediated metastasis suppression. Yeast two-hybrid screen, DARC knockout mouse metastasis model, cell proliferation assays, gene expression analysis Nature medicine High 16862154
2006 DARC on erythrocytes clears angiogenic CXC chemokines (produced by prostate cancer cells) in vitro, reducing endothelial cell chemotaxis; in DARC-deficient mice bearing prostate tumors, intra-tumor angiogenic chemokine concentrations are elevated, tumor vessel density is increased, and tumor growth is greatly augmented. In vitro chemokine clearance assay with wild-type vs. DARC-deficient erythrocytes, transgenic prostate cancer model in DARC KO mice, ELISA, vessel density quantification FASEB journal High 16394268
2007 DARC on endothelial cells attenuates angiogenesis by inducing cellular senescence; in DARC-expressing HCEC cells, capillary formation was initially enhanced then attenuated with cells undergoing senescence, while blocking DARC's N-terminal chemokine-binding domain with anti-Fy6 antibody or adding excess IL-8 increased capillary formation; DARC knockout mice showed more capillary formation in Matrigel plugs. In vitro Matrigel angiogenesis assay, in vivo Matrigel plug assay in DARC KO mice, anti-DARC antibody blocking, IL-8 competition Angiogenesis Medium 17955335
2007 DARC (Darc) regulates bone mineral density (BMD) negatively by promoting osteoclast formation; anti-DARC antibody blocked multinucleated osteoclast formation in vitro; DARC from a high-BMD strain binds chemokines (known to regulate osteoclast formation) with reduced affinity compared to low-BMD strain DARC. QTL mapping, Darc knockout skeletal phenotyping, in vitro osteoclast formation assay with antibody blockade, chemokine binding affinity comparison Genome research Medium 17416748
2009 DARC on red blood cells (RBCs) sequesters CXCL1 from plasma; in DARC-deficient mice, LPS-induced PMN migration into alveolar space was elevated >2-fold with increased alveolar CXCL1 and CXCL2/3, while PMN adhesion to endothelium and interstitial space was reduced; DARC on non-hematopoietic cells had only minor effects in this model. Darc−/− mice, LPS-induced acute lung injury model, bone marrow chimeras distinguishing hematopoietic vs. endothelial DARC, ELISA, flow cytometry European journal of immunology High 19499525
2009 DARC rs12075 (Asp42Gly) non-synonymous polymorphism is a major regulator of erythrocyte DARC-mediated cytokine binding, accounting for ~20% of variability in serum MCP-1 and also regulating IL-8 and RANTES concentrations; clotting and exogenous heparan sulfate release chemokines from DARC, identifying two mechanisms for reservoir chemokine release. Genome-wide association study (n=9598), family-based genetic linkage, quantitative immunoflow cytometry, ex vivo chemokine release assays with heparan sulfate/clotting Blood Medium 20040767
2011 P. vivax Duffy-binding protein RII (RII-PvDBP) dimerization is required for and driven by DARC receptor engagement; crystallographic, solution, and functional studies show that receptor binding induces dimerization; dimerization is required for red blood cell binding and accounts for action of naturally acquired blocking antibodies. X-ray crystallography, solution studies, functional RBC binding assays, antibody blocking experiments Nature structural & molecular biology High 21743458
2014 The DARC N-terminal ectodomain forms an amphipathic helix upon PvDBP-RII binding; crystal structures reveal two DBP-RII molecules sandwiching one or two DARC ectodomains creating heterotrimer/heterotetramer architectures; point mutations of DARC contact residues result in complete loss of RBC binding by DBP-RII; isothermal titration calorimetry shows multi-step binding pathway. NMR epitope mapping, X-ray crystallography (two crystal structures), isothermal titration calorimetry, site-directed mutagenesis, RBC binding assays PLoS pathogens High 24415938
2014 Endothelial DARC mediates abluminal-to-luminal transcytosis of inflammatory chemokines across the blood-brain barrier; erythrocyte DARC functions as a chemokine reservoir determining plasma chemokine levels; endothelial DARC (not erythrocyte DARC) is required for full EAE pathogenesis as shown by bone marrow chimera experiments. In vitro BBB model, Darc−/− mice in EAE model, bone marrow chimeras separating erythrocyte vs. endothelial DARC, chemokine transcytosis assay Brain : a journal of neurology High 24625696
2015 S. aureus hemolytic leukocidins LukED and HlgAB use DARC as their receptor on erythrocytes to mediate lysis; HlgA and LukE bind directly to DARC through different regions; DARC expression level directly correlates with susceptibility to toxin-mediated lysis; DARC overexpression is sufficient to render non-erythroid cells susceptible; LukED and HlgAB support S. aureus hemoglobin acquisition in a DARC-dependent manner. Human erythrocyte DARC polymorphism analysis, DARC overexpression in non-erythroid cells, direct binding assays, hemolysis assays, bacterial growth assays Cell host & microbe High 26320997
2016 DARC on bone marrow macrophages (DARC+ BM macrophages) binds CD82/KAI1 on LT-HSCs and stabilizes CD82 surface expression, promoting TGF-β1/Smad3-mediated CDK inhibitor induction and cell-cycle inhibition; ablation of DARC+ BM macrophages decreased surface CD82 on LT-HSCs, causing cell-cycle entry and differentiation. Cd82−/− mice, macrophage ablation experiments, flow cytometry, TGF-β1/Smad3 signaling analysis, cell cycle assays Cell stem cell High 26996598
2017 DARC (ACKR1) is exquisitely restricted to post-capillary and small collecting venules (not arteries, arterioles, capillaries, veins, or lymphatics) in all murine tissues; DARC is concentrated at endothelial cell-cell junctions; adhesive leukocyte-endothelial interactions are restricted to DARC+ venules as shown by intravital microscopy. Anti-mouse DARC monoclonal antibody generation, immunostaining of murine tissues, intravital microscopy, single-cell suspension analysis BMC biology High 28526034
2017 DARC extracellular domain conformation changes during reticulocyte maturation; although total DARC protein is constant throughout maturation, selective exposure of the DBP-binding site within DARC on CD71high/RNAhigh immature reticulocytes (not mature erythrocytes) explains P. vivax tropism for immature reticulocytes. CD71/RNA flow cytometry of reticulocyte populations, recombinant DBP binding assays, anti-DARC monoclonal antibody binding assays across reticulocyte maturation stages Blood Medium 28754683
2018 ACKR1 is enriched within endothelial junctions of venular walls and presents CXCL2 (produced by transmigrating neutrophils) as a junctional chemokine depot; ACKR1-presented CXCL2 enables efficient unidirectional luminal-to-abluminal neutrophil migration through EC junctions; this pro-migratory activity of CXCL2 depends on ACKR1. Confocal intravital microscopy of cytokine-stimulated mouse cremaster muscles, ACKR1 knockout mice, neutrophil emigration analysis Immunity High 30446388
2019 DARC on endothelial cells is the critical target for S. aureus LukED and HlgAB leukocidin-mediated lethality in mice; these toxins injure primary human endothelial cells in a DARC-dependent manner; mice with DARC-deficient endothelial cells are resistant to toxin-mediated lethality and show reduced tissue damage during bloodstream infection. DARC-deficient endothelial cell mice (conditional KO), toxin challenge experiments, primary human endothelial cell injury assays, S. aureus bloodstream infection model Cell host & microbe High 30799265
2019 DARC on erythrocyte progenitors binds SDF-1 (CXCL12) in a DARC-dependent and conformation-dependent manner; SDF-1 binding is absent on mature erythrocytes due to conformational changes during erythroid development; SDF-1 binding to mature erythrocytes can be induced by pre-treating with IL-8 or specific anti-DARC antibodies that alter DARC conformation. Flow cytometry binding assays with recombinant SDF-1, anti-DARC antibody competition, IL-8 pre-treatment experiments on erythrocytes at different maturation stages Scientific reports Medium 31700087
2021 ACKR1 upregulation in brain microvascular endothelial cells favors transcellular over paracellular T-cell diapedesis across the blood-brain barrier; loss of endothelial ACKR1 reduced transcellular T-cell diapedesis under physiological flow in vitro; ACKR1 is upregulated in venular endothelial cells during EAE. RNA-seq transcriptome profiling of pMBMECs, ACKR1 protein upregulation confirmation, ACKR1 KO in pMBMECs under flow conditions, T-cell diapedesis assay European journal of immunology Medium 34524684
2023 Endothelial ACKR1 expression is induced by contact with neutrophils (not other blood cells) and is regulated by NF-κB; upon removal of blood, ACKR1 protein is rapidly secreted via extracellular vesicles; endogenous ACKR1 does not signal (no response to IL-8 or CXCL1 stimulation confirmed). Primary human lung microvascular endothelial cell culture with whole blood/isolated cell fractions, NF-κB inhibition, extracellular vesicle characterization, IL-8/CXCL1 stimulation signaling assay Frontiers in immunology Medium 37153544
2023 Crystal structure of PvDBP-RII bound to sulphated DARC peptide shows that sulphate on DARC tyrosine 41 binds to a charged pocket on PvDBP-RII; molecular dynamics simulations, affinity measurements, and parasite growth-inhibition experiments confirm importance of this sulphated interaction; the epitope for vaccine-elicited growth-inhibitory antibody DB1 is revealed. X-ray crystallography, molecular dynamics simulations, affinity measurements, parasite growth-inhibition experiments Nature communications High 37336887
2024 ACKR1 in endothelial cells regulates FOLR2+ macrophage migration to injured peritendinous sites; Ackr1−/− bone marrow chimeras showed a decline of FOLR2+ macrophages at the injury site, demonstrating ACKR1-regulated macrophage recruitment is involved in tendon adhesion/regeneration. Single-cell RNA sequencing, bone marrow transplantation chimeras (Lysm-Cre;R26RtdTomato→Ackr1−/− mice), proteomics, in vitro experiments with human cells Bone research Medium 38714649
2024 Endothelial cells with high ACKR1 expression (ACKR1hi ECs) promote aortic dissection (TAAD) through the ACKR1/NF-κB/SPP1 signaling pathway; ACKR1 knockdown suppressed NF-κB signaling and SPP1 expression, reducing macrophage migration and proinflammatory polarization; ACKR1 overexpression exacerbated TAAD; the drug amikacin targets this pathway. Single-cell transcriptomics, gain- and loss-of-function ACKR1 modulation in ECs, NF-κB pathway analysis, macrophage migration/polarization assays, in vivo TAAD mouse model, molecular docking Circulation research Medium 39692014
2010 DARC on Duffy-positive sickle reticulocytes (SRe) maintains α4β1 integrin in a higher chemokine-sensitive affinity state; IL-8 increased Duffy-positive SRe adhesion to VCAM-1 and fibronectin but not Duffy-negative SRe; IL-8 induced α4β1 clustering (not affinity change) in Duffy-positive SRe, demonstrating DARC-dependent modulation of integrin activation state. Static adhesion assays, flow cytometry with conformation-sensitive anti-β1 antibody, immunofluorescence microscopy The Journal of biological chemistry Medium 21088296
2017 DARC expressed in pancreatic cancer cells inhibits CXCR2 signaling and downstream STAT3 activation; DARC knockdown significantly increased cell proliferation in high-DARC cells by activating STAT3; CXCR2-induced STAT3 activation promotes cell cycle progression, inhibits apoptosis, induces angiogenesis, and enhances invasiveness, all of which DARC suppresses by down-regulating CXCR2 signaling. DARC knockdown, CXCR2 knockdown, STAT3 activation assay (EMSA), cell proliferation assays, apoptosis assays, clinical specimen analysis Cytokine Medium 28214673
2024 Anti-ACKR1 autoantibodies from COVID-19 survivors target the N-terminal extracellular domain of ACKR1 on endothelial cells and mediate antibody-dependent cellular cytotoxicity (ADCC) via PBMCs; blocking peptide or liposome ACKR1 recombinant protein alleviated ADCC; purified IgG did not directly trigger apoptosis or increase barrier permeability. Purified IgG from patient plasma, ADCC assay, ACKR1 blocking peptide/recombinant protein, human vein endothelial cell assays, flow cytometry Life science alliance Medium 38740432

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2018 Distinct Compartmentalization of the Chemokines CXCL1 and CXCL2 and the Atypical Receptor ACKR1 Determine Discrete Stages of Neutrophil Diapedesis. Immunity 286 30446388
1995 The Duffy antigen/receptor for chemokines (DARC) is expressed in endothelial cells of Duffy negative individuals who lack the erythrocyte receptor. The Journal of experimental medicine 236 7699323
2006 Interaction of KAI1 on tumor cells with DARC on vascular endothelium leads to metastasis suppression. Nature medicine 185 16862154
2000 Exaggerated response to endotoxin in mice lacking the Duffy antigen/receptor for chemokines (DARC). Blood 172 10961863
2016 CD82/KAI1 Maintains the Dormancy of Long-Term Hematopoietic Stem Cells through Interaction with DARC-Expressing Macrophages. Cell stem cell 135 26996598
2017 Differential DARC/ACKR1 expression distinguishes venular from non-venular endothelial cells in murine tissues. BMC biology 129 28526034
2005 Sulphated tyrosines mediate association of chemokines and Plasmodium vivax Duffy binding protein with the Duffy antigen/receptor for chemokines (DARC). Molecular microbiology 124 15720550
2011 Dimerization of Plasmodium vivax DBP is induced upon receptor binding and drives recognition of DARC. Nature structural & molecular biology 117 21743458
2006 The Duffy antigen/receptor for chemokines (DARC) regulates prostate tumor growth. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 109 16394268
2009 Duffy antigen receptor for chemokines (Darc) polymorphism regulates circulating concentrations of monocyte chemoattractant protein-1 and other inflammatory mediators. Blood 104 20040767
2015 Staphylococcus aureus Targets the Duffy Antigen Receptor for Chemokines (DARC) to Lyse Erythrocytes. Cell host & microbe 97 26320997
2000 Deletion of the murine Duffy gene (Dfy) reveals that the Duffy receptor is functionally redundant. Molecular and cellular biology 91 10757794
2014 Red blood cell invasion by Plasmodium vivax: structural basis for DBP engagement of DARC. PLoS pathogens 90 24415938
2004 Overexpression of the duffy antigen receptor for chemokines (DARC) by NSCLC tumor cells results in increased tumor necrosis. BMC cancer 84 15214968
2017 Population genetic analysis of the DARC locus (Duffy) reveals adaptation from standing variation associated with malaria resistance in humans. PLoS genetics 81 28282382
2003 A high endothelial venule-expressing promiscuous chemokine receptor DARC can bind inflammatory, but not lymphoid, chemokines and is dispensable for lymphocyte homing under physiological conditions. International immunology 78 13679391
2006 Throwing light on DARC. Biochemical Society transactions 70 17073738
2014 DARC shuttles inflammatory chemokines across the blood-brain barrier during autoimmune central nervous system inflammation. Brain : a journal of neurology 63 24625696
2019 Atypical Chemokine Receptor 1 (DARC/ACKR1) in Breast Tumors Is Associated with Survival, Circulating Chemokines, Tumor-Infiltrating Immune Cells, and African Ancestry. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 57 30944146
2005 A structural model of a seven-transmembrane helix receptor: the Duffy antigen/receptor for chemokine (DARC). Biochimica et biophysica acta 56 16046070
2002 Expression of the duffy antigen/receptor for chemokines (DARC) by the inflamed synovial endothelium. The Journal of pathology 56 12081195
2001 Duffy-null promoter heterozygosity reduces DARC expression and abrogates adhesion of the P. vivax ligand required for blood-stage infection. FEBS letters 53 11322957
2012 Construction of an artificial cell membrane anchor using DARC as a fitting for artificial extracellular functionalities of eukaryotic cells. Journal of nanobiotechnology 50 22221512
2011 The association between a Darc gene polymorphism and clinical outcomes in African American patients with acute lung injury. Chest 50 22207676
2008 Duffy (Fy), DARC, and neutropenia among women from the United States, Europe and the Caribbean. British journal of haematology 50 18710383
2002 The Duffy antigen/receptor for chemokines (DARC) and prostate cancer. A role as clear as black and white? FASEB journal : official publication of the Federation of American Societies for Experimental Biology 50 12087071
1998 Binding of HIV-1 to RBCs involves the Duffy antigen receptors for chemokines (DARC). Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 50 9921412
1997 IL-8 single-chain homodimers and heterodimers: interactions with chemokine receptors CXCR1, CXCR2, and DARC. Protein science : a publication of the Protein Society 50 9070443
2021 Detecting retinal cell stress and apoptosis with DARC: Progression from lab to clinic. Progress in retinal and eye research 47 34102318
2009 DARC on RBC limits lung injury by balancing compartmental distribution of CXC chemokines. European journal of immunology 44 19499525
2007 Identification of mouse Duffy antigen receptor for chemokines (Darc) as a BMD QTL gene. Genome research 41 17416748
2017 DARC extracellular domain remodeling in maturating reticulocytes explains Plasmodium vivax tropism. Blood 39 28754683
2010 DARC and D6: silent partners in chemokine regulation? Immunology and cell biology 39 21151196
2003 When renal allografts turn DARC. Transplantation 39 12698093
2018 The Duffy antigen receptor for chemokines, ACKR1,- 'Jeanne DARC' of benign neutropenia. British journal of haematology 37 30592023
2004 Expression of DARC, CXCR3 and CCR5 in giant cell arteritis. Rheumatology (Oxford, England) 37 15572394
2023 Prospects for targeting ACKR1 in cancer and other diseases. Frontiers in immunology 36 37006247
2019 Staphylococcus aureus Leukocidins Target Endothelial DARC to Cause Lethality in Mice. Cell host & microbe 32 30799265
2018 Susceptibility to Plasmodium vivax malaria associated with DARC (Duffy antigen) polymorphisms is influenced by the time of exposure to malaria. Scientific reports 30 30218021
2011 DARC alleles and Duffy phenotypes in African Americans. Transfusion 30 22082243
2011 Species-specific features of DARC, the primate receptor for Plasmodium vivax and Plasmodium knowlesi. Molecular biology and evolution 29 21878684
2009 Expression of Duffy antigen receptor for chemokines (DARC) has no effect on HIV-1 acquisition or progression to AIDS in African Americans. Cell host & microbe 29 19454340
2021 ACKR1 favors transcellular over paracellular T-cell diapedesis across the blood-brain barrier in neuroinflammation in vitro. European journal of immunology 28 34524684
2017 Duffy antigen receptor for chemokines (DARC) expressing in cancer cells inhibits tumor progression by suppressing CXCR2 signaling in human pancreatic ductal adenocarcinoma. Cytokine 28 28214673
2017 Strict tropism for CD71+/CD234+ human reticulocytes limits the zoonotic potential of Plasmodium cynomolgi. Blood 27 28698207
2024 Multi-omics analysis of human tendon adhesion reveals that ACKR1-regulated macrophage migration is involved in regeneration. Bone research 25 38714649
2007 Duffy antigen/receptor for chemokines (DARC) attenuates angiogenesis by causing senescence in endothelial cells. Angiogenesis 24 17955335
2013 Effect of genetic variants in two chemokine decoy receptor genes, DARC and CCBP2, on metastatic potential of breast cancer. PloS one 23 24260134
2012 DARC (Duffy) and BCAM (Lutheran) reduced expression in thyroid cancer. Blood cells, molecules & diseases 23 23168236
2010 Acquired antibody responses against Plasmodium vivax infection vary with host genotype for duffy antigen receptor for chemokines (DARC). PloS one 22 20664684
2018 Long-range haplotype analysis of the malaria parasite receptor gene ACKR1 in an East-African population. Human genome variation 20 30245840
2015 Distinct Transcript Isoforms of the Atypical Chemokine Receptor 1 (ACKR1)/Duffy Antigen Receptor for Chemokines (DARC) Gene Are Expressed in Lymphoblasts and Altered Isoform Levels Are Associated with Genetic Ancestry and the Duffy-Null Allele. PloS one 20 26473357
2024 ACKR1hiECs Promote Aortic Dissection Through Adjusting Macrophage Behavior. Circulation research 18 39692014
2015 DARC: Mapping Surface Topography by Ray-Casting for Effective Virtual Screening at Protein Interaction Sites. Journal of medicinal chemistry 18 26126123
2014 Duffy antigen receptor for chemokine (DARC) polymorphisms and its involvement in acquisition of inhibitory anti-duffy binding protein II (DBPII) immunity. PloS one 17 24710306
2011 Erythrocyte Duffy antigen receptor for chemokines (DARC): diagnostic and therapeutic implications in atherosclerotic cardiovascular disease. Acta pharmacologica Sinica 17 21441947
2022 The DARC Side of Inflamm-Aging: Duffy Antigen Receptor for Chemokines (DARC/ACKR1) as a Potential Biomarker of Aging, Immunosenescence, and Breast Oncogenesis among High-Risk Subpopulations. Cells 16 36497078
2011 The Duffy Antigen/Receptor for Chemokines (DARC) and prostate-cancer risk among Jamaican men. Journal of immigrant and minority health 16 20596779
2025 PDPN+ cancer-associated fibroblasts enhance gastric cancer angiogenesis via AKT/NF-κB activation and the CCL2-ACKR1 axis. MedComm 15 39764562
2015 DARC 2.0: Improved Docking and Virtual Screening at Protein Interaction Sites. PloS one 15 26181386
2006 The DARC conspiracy--virus invasion tactics. Trends in immunology 15 16807107
2015 Distribution of Duffy Antigen Receptor for Chemokines (DARC) and Risk of Prostate Cancer in Barbados, West Indies. Journal of immigrant and minority health 14 24399209
2009 In silico studies on DARC. Infectious disorders drug targets 14 19519483
2023 Endothelial ACKR1 is induced by neutrophil contact and down-regulated by secretion in extracellular vesicles. Frontiers in immunology 13 37153544
2023 Structural basis for DARC binding in reticulocyte invasion by Plasmodium vivax. Nature communications 13 37336887
2018 Deletion of the Duffy antigen receptor for chemokines (DARC) promotes insulin resistance and adipose tissue inflammation during high fat feeding. Molecular and cellular endocrinology 13 29341885
2010 Synthesis of disulfated peptides corresponding to the N-terminus of chemokines receptors CXCR6 (CXCR6 1-20) and DARC (DARC 8-42) using a sulfate-protecting group strategy. Journal of peptide science : an official publication of the European Peptide Society 12 20196090
2010 Activation state of alpha4beta1 integrin on sickle red blood cells is linked to the duffy antigen receptor for chemokines (DARC) expression. The Journal of biological chemistry 12 21088296
2008 HIV and chemokine binding to red blood cells--DARC matters. Cell host & microbe 12 18621004
2016 An introduction to DARC technology. Saudi journal of ophthalmology : official journal of the Saudi Ophthalmological Society 11 28337061
2010 Multiple interests in structural models of DARC transmembrane protein. Transfusion clinique et biologique : journal de la Societe francaise de transfusion sanguine 11 20655787
2006 The DARC side of metastasis: shining a light on KAI1-mediated metastasis suppression in the vascular tunnel. Cancer cell 11 16959609
2024 Clinical and immunological features in ACKR1/DARC-associated neutropenia. Blood advances 10 38039514
2024 Single-cell Transcriptomic Analysis Reveals an Immunosuppressive Network Between POSTN CAFs and ACKR1 ECs in TKI-resistant Lung Cancer. Cancer genomics & proteomics 10 38151287
2020 Deep Analysis of Residue Constraints (DARC): identifying determinants of protein functional specificity. Scientific reports 10 32015389
2019 Neutrophil Effector Functions Are Not Impaired in Duffy Antigen Receptor for Chemokines (DARC)-Null Black South Africans. Frontiers in immunology 10 30972057
2019 Defining Blood Group Gene Reference Alleles by Long-Read Sequencing: Proof of Concept in the ACKR1 Gene Encoding the Duffy Antigens. Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie 10 32110191
2015 Expression of Duffy antigen receptor for chemokines (DARC) is down-regulated in colorectal cancer. Journal of receptor and signal transduction research 10 26096170
2020 ACKR1 Alleles at 5.6 kb in a Well-Characterized Renewable US Food and Drug Administration (FDA) Reference Panel for Standardization of Blood Group Genotyping. The Journal of molecular diagnostics : JMD 9 32688055
2012 Molecular evolution of a malaria resistance gene (DARC) in primates. Immunogenetics 9 22395823
2019 Impact of DARC rs12075 Variants on Liver Fibrosis Progression in Patients with Chronic Hepatitis C: A Retrospective Study. Biomolecules 8 30970632
2019 Differential interaction between DARC and SDF-1 on erythrocytes and their precursors. Scientific reports 8 31700087
2009 CCR5 signalling, but not DARC or D6 regulatory, chemokine receptors are targeted by herpesvirus U83A chemokine which delays receptor internalisation via diversion to a caveolin-linked pathway. Journal of inflammation (London, England) 8 19643012
2019 Duffy antigen receptor for chemokines (DARC) and susceptibility to Plasmodium vivax malaria. Parasitology international 7 30928426
2006 [Downregulation of Duffy antigen receptor for chemokine (DARC) is associated with lymph node metastasis in human breast cancer]. Zhonghua zhong liu za zhi [Chinese journal of oncology] 7 17236552
2015 Studies of a murine monoclonal antibody directed against DARC: reappraisal of its specificity. PloS one 6 25706384
2011 The DARC site: a database of aligned ribosomal complexes. Nucleic acids research 6 22009674
2010 A Duffy antigen receptor for chemokines (DARC) polymorphism that determines pro-fibrotic chemokine serum concentrations is not directly associated with severity of hepatitis C infection. Human immunology 6 21156192
2009 Characterization and transcriptional analysis of the promoter region of the Duffy blood group, chemokine receptor (DARC) gene in cattle. Veterinary immunology and immunopathology 6 19559488
2020 The DARC-null trait is associated with moderate modulation of NK cell profiles and unaltered cytolytic T cell profiles in black South Africans. PloS one 5 33211774
2018 Engagement Rules That Underpin DBL-DARC Interactions for Ingress of Plasmodium knowlesi and Plasmodium vivax Into Human Erythrocytes. Frontiers in molecular biosciences 5 30211170
2001 Duffy antigen/receptor for chemokines (DARC): genotypes in Ashkenazi and non-Ashkenazi Jews in Israel. Human biology 5 11446431
2025 Single-cell transcriptomic analysis deciphers the inflammatory microenvironment characterized by CXCL9+ fibroblasts and ACKR1+ endothelial cells in immune-related myocarditis. Journal of translational medicine 4 40380233
2025 Investigating the interaction of ACKR1 and c-Myc in the breast carcinoma tumor microenvironment modulation. Discover oncology 4 40853589
2024 Inflammatory risk contributes to post-COVID endothelial dysfunction through anti-ACKR1 autoantibody. Life science alliance 4 38740432
2016 Potential Role of DARC-Chemokine Interaction in the Recruitment of Osteoclast Precursors in Response to Bacterial Lipopolysaccharide Challenge. Calcified tissue international 4 27376530
2011 Evidence that erythrocyte DARC-positive phenotype can affect the GVHD occurrence after HLA-identical sibling HSCT. Transplant immunology 4 21784153
2022 Ancestry, ACKR1 and leucopenia in patients with systemic lupus erythematosus. Lupus science & medicine 3 36376015
2021 Cataloguing experimentally confirmed 80.7 kb-long ACKR1 haplotypes from the 1000 Genomes Project database. BMC bioinformatics 3 34039276
2015 A genetic marker of the ACKR1 gene is present in patients with Type II congenital smell loss who have type I hyposmia and hypogeusia. American journal of otolaryngology 3 27968956

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