Affinage

CCR3

C-C chemokine receptor type 3 · UniProt P51677

Length
355 aa
Mass
41.0 kDa
Annotated
2026-06-09
100 papers in source corpus 40 papers cited in narrative 38 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CCR3 is a Gαi-coupled CC chemokine receptor that serves as the central effector receptor for eotaxins (CCL11/CCL24/CCL26) and related CC chemokines, driving eosinophil chemotaxis, degranulation, and tissue accumulation that underlie allergic and remodeling pathology (PMID:10984371, PMID:16210640). High-affinity ligand engagement is governed by the receptor N-terminus: residues 1–35, and particularly two sulfotyrosines in the DDYY-containing region around residues 8–23, form the primary chemokine-binding surface through hydrophobic, salt-bridge, and cation-π contacts that are oriented distinctly from CXC-receptor complexes (PMID:10859315, PMID:25450766). Agonist activation and small-molecule antagonist binding both converge on transmembrane residues Tyr-41, Tyr-113, and Glu-287, where the Y113A mutation can convert an antagonist into an agonist, while intracellular loop 2 contacts revealed by cryo-EM are the critical determinant of G-protein coupling (PMID:17635911, PMID:35570218); cholesterol acts as a positive allosteric modulator that enhances CCL11 affinity and stimulates Gαi3 GTPase activity (PMID:34490352). Downstream, CCR3 signals through Gαi-dependent PI3K, ERK, and p38 MAPK, with cell spreading via β1/β2 integrins required for eosinophil RNase secretion, and EGFR transactivation contributing to MAP-kinase and IL-8 responses in epithelium (PMID:23742707, PMID:15219825). Beyond eosinophils, functional CCR3 is expressed on Th2 cells, platelets, airway epithelial and smooth muscle cells, dermal fibroblasts, and vascular endothelium, where it mediates migration, wound repair, fibrosis, and neovascularization (PMID:9302298, PMID:9480044, PMID:15130922, PMID:16920975, PMID:19525930, PMID:23702389), and on CD4+ cells and microglia it acts as an HIV-1 co-receptor whose usage depends on the gp120 V3 region (PMID:8674119, PMID:8674120, PMID:9024664). Genetic eotaxin/CCR3 epistasis in mouse asthma models establishes its non-redundant requirement for allergen- and IL-13-driven airway eosinophilia and remodeling (PMID:16210640, PMID:17148674).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1996 High

    Established that CCR3 has a function beyond chemokine signaling by acting as an HIV-1 entry co-receptor, defining a host-pathogen role for the receptor.

    Evidence CCR3/CD4 co-expression infectivity assay with eotaxin competition and V3-dependent isolate mapping

    PMID:8674119 PMID:8674120

    Open questions at the time
    • Restricted to a subset of HIV-1 isolates
    • Physiological relevance relative to CCR5 in vivo not resolved
  2. 1997 High

    Defined CCR3 co-receptor function in primary CNS cells, extending HIV-1 entry relevance to microglia.

    Evidence Primary microglial infection with anti-CCR3 antibody and eotaxin blocking

    PMID:9024664

    Open questions at the time
    • Relative contribution of CCR3 versus CCR5 in CNS infection unquantified
  3. 1997 High

    Showed CCR3 is selectively expressed on Th2 cells and functionally couples eotaxin to calcium flux and chemotaxis, linking the receptor to the Th2 axis of allergic immunity.

    Evidence Antibody-based Th2 isolation, Ca2+ measurement, and chemotaxis assays

    PMID:9302298 PMID:9480044

    Open questions at the time
    • Transcriptional control of Th2-selective expression not addressed
  4. 1999 High

    Determined that eosinophil degranulation is mediated exclusively through CCR3, separating effector (granule release) from generic calcium signaling and establishing CCR3 as the key eosinophil effector receptor.

    Evidence Ca2+ flux, eosinophil-derived neurotoxin RIA, and antibody blocking on purified eosinophils with multiple ligands

    PMID:10984371

    Open questions at the time
    • Signaling steps coupling CCR3 to granule exocytosis not defined here
  5. 2000 High

    Mapped the eotaxin-binding surface to the CCR3 N-terminal region, providing the first structural basis for ligand recognition.

    Evidence Synthetic peptide binding screens and NMR characterization of the eotaxin–CCR3 N-terminus interface

    PMID:10859315

    Open questions at the time
    • Does not address transmembrane activation determinants
    • Post-translational modification of the N-terminus not yet defined
  6. 2000 Medium

    Extended functional CCR3 expression to platelets, broadening its role beyond leukocyte chemotaxis to hemostatic activation.

    Evidence RT-PCR, flow cytometry, Ca2+, aggregation/granule release assays with glycosaminoglycan cleavage

    PMID:11110672

    Open questions at the time
    • In vivo platelet relevance not established
    • Single lab
  7. 2001 High

    Demonstrated functional CCR3 on airway epithelium coupling eotaxin to pertussis-toxin-sensitive Gi signaling and tyrosine phosphorylation, implicating non-hematopoietic cells in CCR3 biology.

    Evidence Northern/Western blot, Ca2+ flux, tyrosine phosphorylation, radioligand binding, pertussis toxin and antibody blocking

    PMID:11160184

    Open questions at the time
    • Downstream transcriptional outputs not fully mapped here
  8. 2003 High

    Revealed cross-regulation between chemokine systems by showing CXCR3 ligands antagonize CCR3 and that CCL11/CXCL11 share overlapping CCR3 extracellular binding sites.

    Evidence Ca2+ flux, chemotaxis, CCR3-CCR1 chimeric receptors, and radioligand binding

    PMID:12884299

    Open questions at the time
    • Physiological significance of cross-receptor antagonism in vivo unclear
  9. 2005 High

    Established the non-redundant, hierarchical requirement of CCR3 and its eotaxin ligands for allergen-induced airway eosinophilia using genetic epistasis.

    Evidence Eotaxin-1/2 and CCR3 knockout combinations in an OVA asthma model with BAL and tissue eosinophil counts

    PMID:16210640

    Open questions at the time
    • Tissue-compartment-specific ligand contributions only partly resolved
  10. 2005 High

    Linked CCR3-driven eosinophil recruitment to airway nerves and M2 muscarinic dysfunction, connecting the receptor to airway hyperresponsiveness mechanistically.

    Evidence Guinea pig antigen challenge with CCR3 antagonist, vagal/M2R functional assays, and cytokine-stimulated neuron culture

    PMID:16374515

    Open questions at the time
    • Molecular signal for nerve-directed eosinophil clustering not defined
  11. 2006 High

    Showed CCR3 is required for IL-13-driven airway remodeling, extending its role from cell recruitment to structural tissue changes.

    Evidence IL-13 transgenic × CCR3-deficient crosses with histology and ΔdblGATA eosinophil-deficient controls

    PMID:17148674

    Open questions at the time
    • Whether remodeling is fully eosinophil-dependent versus direct CCR3 action unresolved
  12. 2007 High

    Identified the transmembrane residues (Tyr-41, Tyr-113, Glu-287) shared by agonists and antagonists, defining the small-molecule pharmacophore and an agonist/antagonist switch at Y113.

    Evidence Site-directed mutagenesis, CCR3-CCR1 chimeras, chemotaxis and Ca2+ assays

    PMID:17635911

    Open questions at the time
    • No high-resolution ligand-bound structure at the time
  13. 2009 High

    Uncovered an eosinophil-independent CCR3 role on choroidal neovascular endothelium, repositioning the receptor as a target in age-related macular degeneration.

    Evidence Human AMD immunohistochemistry, mouse CNV genetic/pharmacological targeting, endothelial proliferation assays, cell-type-deficient mouse controls

    PMID:19525930

    Open questions at the time
    • Endothelial CCR3 signaling pathway in angiogenesis not detailed
  14. 2013 Medium

    Defined the Gαi→PI3K/ERK/p38 signaling and integrin-dependent spreading required for CCR3-driven eosinophil RNase secretion, mapping the effector signaling cascade.

    Evidence RNase activity assays in mouse and human eosinophils with pathway inhibitors and integrin-blocking antibodies

    PMID:23742707

    Open questions at the time
    • Single lab
    • Spatial coordination of integrin and CCR3 signaling not resolved
  15. 2014 High

    Established that tyrosine sulfation of the CCR3 N-terminus is a critical determinant of high-affinity eotaxin binding, defining a post-translational regulatory layer of ligand recognition.

    Evidence NMR structure of CCL11 bound to sulfo-CCR3(8-23) with functional sulfation validation

    PMID:25450766

    Open questions at the time
    • Regulation of CCR3 sulfation in vivo not addressed
  16. 2018 High

    Demonstrated biased antagonism of CCR3, showing a peptide nanoparticle can selectively inhibit early ERK signaling while promoting receptor internalization, refining therapeutic targeting concepts.

    Evidence NMR binding, time-resolved ERK Western blot, confocal internalization, and in vivo allergen asthma model

    PMID:29778505

    Open questions at the time
    • β-arrestin-associated late signaling consequences in disease not fully mapped
  17. 2021 Medium

    Identified cholesterol as a positive allosteric modulator coupling membrane lipid environment to CCR3 ligand affinity and Gαi3 GTPase output.

    Evidence Reconstituted recombinant CCR3 in SMALPs/proteoliposomes with affinity and Gαi3 GTPase assays

    PMID:34490352

    Open questions at the time
    • In vitro reconstitution only
    • Cellular cholesterol modulation of CCR3 not tested
  18. 2022 High

    Provided a cryo-EM structure establishing ICL2 as the principal determinant of CCR3 G-protein coupling, defining the activation architecture.

    Evidence Apo-state cryo-EM structure with functional mutagenesis

    PMID:35570218

    Open questions at the time
    • No ligand- or G-protein-bound active-state structure reported here

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CCR3's broad non-eosinophil functions (endothelial angiogenesis, fibroblast/cardiac fibrosis, tumor invasion, neuronal hyperexcitability, age-related cognitive decline) are encoded by distinct ligand-, cell-type-, or biased-signaling programs remains unresolved.
  • Cell-type-specific downstream signaling not unified
  • Whether distinct ligands (CCL7, CCL8, CCL24, CCL26) bias different outcomes is unclear
  • Active-state structures with diverse ligands lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 4 GO:0001618 virus receptor activity 2 GO:0098772 molecular function regulator activity 1
Localization
GO:0005886 plasma membrane 4
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3 R-HSA-168256 Immune System 3
Partners
CCL11CCL24CCL26CCL7CCL8CD4EGFRGNAI3

Evidence

Reading pass · 38 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 CCR3, when co-expressed with CD4 on otherwise non-permissive cells, functions as a co-receptor for entry by a restricted subset of primary HIV-1 isolates; binding of the CCR3 ligand eotaxin inhibits HIV-1 infection, and co-receptor usage depends on the V3 region of gp120. Cell-based infectivity assay with CCR3-transfected cell lines co-expressing CD4; ligand competition experiment Cell High 8674119 8674120
1997 CCR3 and CCR5 are both expressed on brain microglia and serve as co-receptors for HIV-1 infection of these CNS cells; the CCR3 ligand eotaxin and anti-CCR3 antibody inhibited HIV-1 infection of microglia. Primary microglial infection assay; antibody/ligand blocking experiments Nature High 9024664
1997 CCR3 is selectively expressed on human Th2 (but not Th1) cells; eotaxin stimulation of CCR3+ T cells induces intracellular calcium increase and chemotaxis. Anti-CCR3 antibody-based cell isolation; intracellular calcium measurement; chemotaxis assay Science High 9302298 9480044
1997 CCR3 function (eotaxin binding and CCR3-mediated calcium mobilization and eosinophil chemotaxis) is markedly sensitive to small changes in extracellular pH and ionic strength (NaCl concentration) within physiological and near-physiological ranges. Radioligand binding assay; Ca2+ mobilization assay; in vitro eosinophil chemotaxis assay The Journal of biological chemistry Medium 9353270
1999 IFN-γ treatment of human neutrophils induces CCR3 (and CCR1) mRNA and surface expression, enabling functional chemotactic responses to eotaxin; an anti-CCR3 monoclonal antibody (7B11) blocked this eotaxin-induced chemotaxis. RT-PCR; radioligand binding; in vitro chemotaxis assay with blocking mAb Journal of immunology Medium 9886422
1999 Chemokine-induced eosinophil degranulation (eosinophil-derived neurotoxin release) is mediated exclusively through CCR3; non-CCR3 ligands that induce calcium influx do not induce degranulation, and anti-CCR3 antibody significantly inhibited CCR3-ligand-induced degranulation. Ca2+ flux assay; RIA for eosinophil-derived neurotoxin; antibody blocking experiments on purified eosinophils The Journal of allergy and clinical immunology High 10984371
1999 Met-RANTES acts as an antagonist of human eosinophil effector functions (Ca2+ transients, actin polymerization, reactive oxygen species release) through CCR1 preferentially over CCR3; eotaxin-induced responses via CCR3 were only partially blocked at concentrations that fully blocked RANTES/MCP-3 responses. Ca2+ flux assay; actin polymerization assay; reactive oxygen species assay; dose-response antagonism with Met-RANTES on purified eosinophils European journal of immunology Medium 9394815
2000 The N-terminal region of CCR3 (residues 1–35, especially the DDYY-containing central region around residues 8–23) is the primary binding surface for eotaxin; the N-loop, 3(10)-helical turn, and β2-β3 hairpin of eotaxin form the complementary receptor-binding groove. Synthetic peptide binding screens; NMR spectroscopy (1H-15N HSQC, 2D/3D homonuclear NMR, 15N-filtered TOCSY); dissociation constant measurement The Journal of biological chemistry High 10859315
2000 CCR3 is functionally expressed on human platelets; eotaxin activates platelets via CCR3, inducing Ca2+ signals, aggregation, and granule release; these responses are partially dependent on secondary ADP release and are inhibited by cleavage of heparan/chondroitin sulfate on the platelet surface. RT-PCR; flow cytometry; immunoprecipitation/Western blot; Ca2+ measurement; aggregation and granule release assays; glycosaminoglycan cleavage experiments Blood Medium 11110672
2000 CCL11 (eotaxin) induces CCR3-dependent smooth muscle cell (SMC) chemotaxis and migration; anti-CCR3 antibody (but not anti-CCR2) blocked SMC migration; CCR3 is upregulated in medial SMCs after arterial injury in a pattern consistent with a migratory phenotype. RT-PCR; Western blot; flow cytometry; Boyden chamber chemotaxis assay; scrape-wound assay; antibody blocking; in vivo mouse femoral artery injury model with immunostaining Arteriosclerosis, thrombosis, and vascular biology High 15130922
2001 CCR3 is functionally expressed on airway epithelial cells; eotaxin stimulates intracellular Ca2+ flux and tyrosine phosphorylation of cellular proteins via epithelial CCR3; these signals are blocked by anti-CCR3 mAb (7B11) or pertussis toxin, and 125I-eotaxin binding confirms expected ligand specificity. Northern blot; Western blot; flow cytometry; Ca2+ flux assay; tyrosine phosphorylation assay; radioligand binding; pertussis toxin treatment; antibody blocking Journal of immunology High 11160184
2001 IL-3 induces dose- and time-dependent down-regulation of CCR3 surface expression and mRNA in human eosinophils; this down-regulation is prevented by anti-IL-3 antibody and by phenylarsine oxide (an inhibitor of receptor internalization), and is partially inhibited by the PI3K inhibitor wortmannin, indicating a distinct internalization mechanism from eotaxin-induced down-regulation. Flow cytometry; RT-PCR; Ca2+ flux assay; pharmacological inhibition (wortmannin, phenylarsine oxide); blocking antibody Journal of immunology Medium 11544337
2001 Eotaxin induces differentiation of eosinophils from CD34+ cord blood progenitor cells via CCR3 (which is expressed and functional on these progenitors); this differentiation is IL-3-, IL-5-, and GM-CSF-independent, and Th2 cytokines up-regulate CCR3 surface expression on progenitors while IL-12/IFN-γ decreases it. In situ RT-PCR; immunostaining; flow cytometry; Ca2+ mobilization assay; in vitro eosinophil differentiation culture with neutralizing antibodies Journal of immunology Medium 12496441
2003 CXCR3 ligands (CXCL9, CXCL10, CXCL11) inhibit CCR3-mediated functional responses (chemotaxis and Ca2+ flux) in human eosinophils and CCR3 transfectants induced by all three eotaxins; CXCL11 is the most efficacious antagonist. CCR3-CCR1 chimeric receptor studies revealed that CCL11 and CXCL11 share overlapping binding sites within CCR3 extracellular loops. Additionally, CCL11 binds with high affinity to CXCR3 (acting as a potential decoy receptor). Ca2+ flux assay; eosinophil chemotaxis assay; CCR3-CCR1 chimeric receptor constructs; radioligand binding European journal of immunology High 12884299
2003 CCR3 ligation by eotaxin/CCL11 induces apoptosis in IL-2/IL-4-stimulated B cells via upregulation of CD95 and CD95L, triggering a caspase cascade; this apoptotic effect is distinct from chemotaxis (CCR3 ligation does not induce chemotaxis or adhesion in these cells). Flow cytometry; apoptosis assays; cytochrome c release measurement; caspase activity assays; CD95/CD95L expression analysis in primary B cells and B cell lines Journal of immunology Medium 12902471
2004 CCR3 activation by eotaxin in bronchial epithelial cells (NCI-H292) leads to transactivation of EGFR (tyrosine phosphorylation of EGFR); EGFR inhibition (AG1478) blocks CCR3-induced MAP kinase phosphorylation and IL-8 production. Tyrosine phosphorylation assay; EGFR inhibitor (AG1478) treatment; MAP kinase phosphorylation assay; IL-8 ELISA Biochemical and biophysical research communications Medium 15219825
2005 Eotaxin and CCR3-deficient mice show profound reduction of allergen-induced eosinophil recruitment to the airway lumen and loss of organized peribronchial/perivascular eosinophil accumulation; eotaxin-1/2 double-knockout approaches CCR3-deficiency levels, demonstrating a hierarchical and synergistic role for multiple CCR3 ligands in pulmonary eosinophilia. Genetic knockout mouse models (eotaxin-1, eotaxin-2, eotaxin-1/2 double KO, CCR3 KO); OVA-induced experimental asthma model; bronchoalveolar lavage analysis; tissue eosinophil counting Journal of immunology High 16210640
2005 CCR3 signaling mediates recruitment of eosinophils specifically to airway nerves (not overall tissue eosinophilia); CCR3 antagonist (GW701897B) prevented eosinophil clustering around nerves, preserved inhibitory M2 muscarinic receptor function, and abrogated airway hyperresponsiveness. Eotaxin is produced by airway parasympathetic neurons and is upregulated by IL-4 and IL-13. In vivo guinea pig antigen challenge model; CCR3 antagonist treatment; vagal stimulation assay; M2R function assay; immunostaining; cultured airway neurons + neuroblastoma cells with cytokine stimulation The Journal of clinical investigation High 16374515
2005 CCR3 is functionally expressed on asthmatic airway smooth muscle cells (ASMC) at higher levels than in non-asthmatic subjects; TNF-α increases CCR3 surface expression; eotaxin induces Ca2+ mobilization and significant chemotaxis of ASMC via CCR3. RT-PCR; FACS; Ca2+ assay; in vitro Boyden chamber chemotaxis assay; TNF-α stimulation Journal of immunology Medium 16081847
2006 CCR3 activation in airway epithelial cells by eotaxins (CCL11, CCL24, CCL26) drives wound closure, cell proliferation, and chemotaxis; CCL11 also up-regulates profibrogenic molecules (FGF-1, FGF-5) and multiple CC/CXC chemokines; all effects are selectively inhibited by a CCR3 antagonist. In vitro wound repair assay; fluorometric proliferation and chemotaxis assays; pathway-specific cDNA arrays; CCR3 antagonist treatment Journal of immunology Medium 16920975
2006 IL-13 transgenic lung overexpression-driven eosinophil recruitment and airway remodeling (mucus metaplasia, collagen deposition) require CCR3; CCR3-deficient mice crossed with IL-13 transgenics show 98% reduction in lung eosinophils and marked attenuation of remodeling, correlating with changes in pulmonary TGF-β1 and protease expression. Genetic cross of IL-13 lung-inducible transgenic mice with CCR3-deficient mice; histological and biochemical analysis of remodeling markers; eosinophil-deficient (ΔdblGATA) mouse controls The American journal of pathology High 17148674
2007 Transmembrane residues Tyr-41, Tyr-113, and Glu-287 of CCR3 are critical for both antagonist (UCB35625) binding and receptor activation by CCL11/eotaxin; mutation Y113A abolishes antagonist binding and converts UCB35625 from antagonist to agonist; a novel specific CCR3 agonist (CH0076989) interacts with the same transmembrane residues and does not require the CCR3 N-terminus. Site-directed mutagenesis; CCR3-CCR1 chimeric receptor constructs; cell-based chemotaxis assay; Ca2+ flux assay The Journal of biological chemistry High 17635911
2009 CCR3 is specifically expressed on choroidal neovascular endothelial cells in human AMD; genetic or pharmacological targeting of CCR3 or its eotaxin ligands inhibits injury-induced CNV in mice; CCR3 blockade directly inhibits endothelial cell proliferation and is uncoupled from eosinophil/mast cell inflammation. Immunohistochemistry on human AMD tissue; CCR3 gene knockout and pharmacological inhibition in mouse CNV models; endothelial proliferation assay; quantum dot in vivo imaging; comparison with eosinophil- and mast cell-deficient mice Nature High 19525930
2011 CCL11 activates CCR3 on anaplastic large cell lymphoma (ALCL) cells in an autocrine manner, promoting cell survival via ERK1/2 phosphorylation and upregulation of anti-apoptotic proteins Bcl-xL and survivin; ERK inhibition completely blocked CCL11-promoted survival. Cell survival and proliferation assays; ERK1/2 phosphorylation (Western blot); anti-apoptotic protein expression; ERK inhibitor treatment; in vivo tumor growth assay Cancer research Medium 21406396
2013 CCR3-mediated secretion of eosinophil-associated RNases (EARs) in mouse and human eosinophils requires Gαi-dependent signaling through PI3K, ERK, and p38 MAPK; β1 and β2 integrins are also required, with cell spreading being obligatory for EAR secretion. RNase activity assay on primary mouse and human eosinophils; specific pathway inhibitors (PI3K, ERK, p38 MAPK inhibitors); integrin-blocking antibodies; microscopy for cell adhesion/spreading Allergy Medium 23742707
2013 CCL26 (eotaxin-3) induces CCR3 signaling in human dermal fibroblasts (which express CCR3 abundantly), resulting in intracellular Ca2+ mobilization, enhanced fibroblast migration, and wound repair capacity, but no proliferation; this provides a CCR3-mediated epidermis-to-dermis communication pathway in atopic skin inflammation. Flow cytometry and immunofluorescence for CCR3 on fibroblasts; Ca2+ mobilization assay; cell migration and repair assays; cell proliferation assay; real-time PCR for CCL26 Journal of dermatological science Medium 23702389
2014 Tyrosine sulfation of CCR3 N-terminal residues (specifically two sulfotyrosines in residues 8–23) dramatically enhances binding to CCL11/eotaxin-1; structural analysis reveals sulfotyrosine residues form hydrophobic, salt bridge, and cation-π interactions with conserved residues in CC chemokines. The orientation of CCR3 N-terminus relative to the chemokine differs substantially from CXC chemokine receptor complexes. NMR structure determination of CCL11 bound to sulfo-CCR3(8-23) peptide; functional receptor activity assays confirming intact CCR3 sulfation; binding affinity measurement Structure High 25450766
2014 Eotaxin-1 (CCL11) promotes prostate cancer cell invasion and migration via the CCR3-ERK pathway, leading to upregulation of MMP-3; siRNA knockdown of CCR3 inhibits invasion and attenuates eotaxin-1-induced ERK1/2 activation and MMP-3 expression; MEK inhibition (U0126) similarly suppresses invasion. siRNA knockdown of CCR3; invasion/migration assays; ERK1/2 phosphorylation (Western blot); MMP-3 mRNA (RT-PCR) and protein (ELISA); MEK inhibitor (U0126) Oncology reports Medium 24604010
2016 CCL7 interacts with CCR3 in colon cancer cells to promote cellular proliferation, invasion, and migration via the ERK and JNK signaling pathways; CCL7-overexpressing cells formed faster ectopic tumors and developed liver/lung metastases in orthotopic mouse models. CCL7-overexpressing cell lines; in vitro proliferation, invasion, and migration assays; ectopic and orthotopic mouse models; signaling pathway analysis (ERK, JNK) Oncotarget Medium 27167205
2017 CCL8 binds directly to CCR3 with a KD of ~1.2 × 10−7 M (measured by quartz crystal microbalance); CCL8 induces CCR3 internalization in vivo and has a weaker chemotactic effect compared to CCL11 and CCL24 on CCR3-expressing cells. Quartz crystal microbalance (QCM) binding assay; receptor internalization assay (flow cytometry); chemotaxis assay BMC immunology Medium 29281969
2018 A peptide nanoparticle CCR3 antagonist (R321) binds directly to CCR3, inhibits only the early phase of ERK1/2 activation (not the late β-arrestin-associated phase), promotes CCR3 internalization and degradation (biased antagonism), and blocks eosinophil recruitment and airway hyperresponsiveness in a mouse asthma model. Dynamic light scattering; NMR binding analysis; flow cytometry; confocal microscopy; ERK1/2 Western blot (time-course); in vivo triple-allergen mouse asthma model The Journal of allergy and clinical immunology High 29778505
2021 Cholesterol acts as a dose-dependent positive allosteric modulator of CCR3 function: increasing cholesterol concentration enhances CCR3 affinity for CCL11 (in both SMALPs and proteoliposomes), and this heightened receptor activation directly increases GTPase activity of the associated Gαi3 protein. Recombinant CCR3 production in E. coli; reconstitution into SMALPs and proteoliposomes; ligand affinity measurement; Gαi3 GTPase activity assay Frontiers in molecular biosciences Medium 34490352
2022 Cryo-EM structure of CCR3 in the apo state reveals that interactions around intracellular loop 2 (ICL2) of CCR3 are critical and conserved for G-protein activation; these interactions play a more critical role in G-protein coupling than those around ICL3. Cryo-electron microscopy; structure determination; functional mutagenesis experiments Cell discovery High 35570218
2022 Conditional knockout of bone marrow CCR3 in mice reduces eosinophilic inflammation and Th2 immune response in an OVA-induced allergic rhinitis model; this is mechanistically linked to inhibition of the PI3K/AKT signaling pathway downstream of CCR3. Cre-LoxP conditional knockout; OVA-induced AR mouse model; PI3K/AKT pathway inhibitor (Ly294002); histopathology; eosinophil counting; cytokine ELISA Scientific reports Medium 35354939
2022 The CCL24/CCR3 axis stimulates M2 macrophage polarization and cardiac fibroblast activation via CCR3's G protein-coupled receptor function; blocking CCL24 prevents Ang II-induced cardiac hypertrophy and fibrosis; in vitro experiments confirmed CCL24 promotes activation and migration of cardiac fibroblasts via CCR3. Co-IP; ChIP; CCL24 antibody blockade in vivo (Ang II mouse model); single-cell CyTOF; in vitro fibroblast activation/migration assays; immunofluorescence co-localization Cell biology and toxicology Medium 36131165
2023 CCR3-expressing T cells in the periphery mediate age-related cognitive decline and neuroinflammation; CCR3 inhibition prevents infiltration of CCR3+ T cells across the blood-brain barrier, reducing neuroinflammation. The pro-cognitive benefit of CCR3 inhibition is not due to direct action on CNS-resident cells. CCR3 inhibition in aged mice; behavioral cognitive testing; T-cell infiltration analysis; blood-brain barrier assessment Communications biology Medium 36934154
2023 IgE directly promotes eosinophil migration in chronic rhinosinusitis by upregulating CCR3 expression on eosinophils; this effect is mediated through CD23 (FcεRII) on eosinophils, as lumiliximab (anti-CD23) restrains IgE-induced CCR3-dependent migration. Flow cytometry; immunohistochemistry/immunofluorescence; functional eosinophil migration assay; antibody blockade (omalizumab, lumiliximab) The Journal of allergy and clinical immunology Medium 37922997
2023 CCR3 mediates CCL7-induced neuronal hyperexcitability and ERK activation in trigeminal ganglion neurons; selective CCR3 antagonist (intra-TG injection) alleviates trigeminal neuropathic pain and reduces ERK phosphorylation; CCR3 is co-expressed with CCR2 on TG neurons. Real-time qPCR; immunofluorescence; Western blot (ERK phosphorylation); whole-cell patch clamp recording; selective receptor antagonists (intra-TG injection); behavioral pain testing Molecular pain Medium 36998150

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1996 The beta-chemokine receptors CCR3 and CCR5 facilitate infection by primary HIV-1 isolates. Cell 2054 8674119
1996 A dual-tropic primary HIV-1 isolate that uses fusin and the beta-chemokine receptors CKR-5, CKR-3, and CKR-2b as fusion cofactors. Cell 1669 8674120
1997 Selective expression of the eotaxin receptor CCR3 by human T helper 2 cells. Science (New York, N.Y.) 818 9302298
1997 CCR3 and CCR5 are co-receptors for HIV-1 infection of microglia. Nature 778 9024664
1999 T helper cell type 2 cytokine-mediated comitogenic responses and CCR3 expression during differentiation of human mast cells in vitro. The Journal of experimental medicine 267 10432289
1997 Functional expression of the eotaxin receptor CCR3 in T lymphocytes co-localizing with eosinophils. Current biology : CB 218 9480044
2000 Overexpression of eotaxin and the CCR3 receptor in human atherosclerosis: using genomic technology to identify a potential novel pathway of vascular inflammation. Circulation 206 11056090
2009 CCR3 is a target for age-related macular degeneration diagnosis and therapy. Nature 202 19525930
2000 Functional expression of CCR1, CCR3, CCR4, and CXCR4 chemokine receptors on human platelets. Blood 201 11110672
2005 The eotaxin chemokines and CCR3 are fundamental regulators of allergen-induced pulmonary eosinophilia. Journal of immunology (Baltimore, Md. : 1950) 190 16210640
1999 Up-regulation of CCR1 and CCR3 and induction of chemotaxis to CC chemokines by IFN-gamma in human neutrophils. Journal of immunology (Baltimore, Md. : 1950) 168 9886422
2000 Expression of the beta-chemokine receptors CCR2, CCR3 and CCR5 in multiple sclerosis central nervous system tissue. Journal of neuroimmunology 162 10900353
1999 Enhanced expression of eotaxin and CCR3 in atopic dermatitis. The Journal of investigative dermatology 154 10417617
1999 Differential regulation of eosinophil chemokine signaling via CCR3 and non-CCR3 pathways. Journal of immunology (Baltimore, Md. : 1950) 152 10072545
2001 Interleukin-5 induces CD34(+) eosinophil progenitor mobilization and eosinophil CCR3 expression in asthma. American journal of respiratory and critical care medicine 111 11704586
2005 Neuronal eotaxin and the effects of CCR3 antagonist on airway hyperreactivity and M2 receptor dysfunction. The Journal of clinical investigation 110 16374515
2003 CCR3 functional responses are regulated by both CXCR3 and its ligands CXCL9, CXCL10 and CXCL11. European journal of immunology 108 12884299
2000 Chemokines induce eosinophil degranulation through CCR-3. The Journal of allergy and clinical immunology 108 10984371
2005 Role of Eotaxin-1 (CCL11) and CC chemokine receptor 3 (CCR3) in bleomycin-induced lung injury and fibrosis. The American journal of pathology 97 16314464
2001 Expression of the C-C chemokine receptor CCR3 in human airway epithelial cells. Journal of immunology (Baltimore, Md. : 1950) 96 11160184
1997 The CC chemokine antagonist Met-RANTES inhibits eosinophil effector functions through the chemokine receptors CCR1 and CCR3. European journal of immunology 91 9394815
2016 Crosstalk between CCL7 and CCR3 promotes metastasis of colon cancer cells via ERK-JNK signaling pathways. Oncotarget 90 27167205
2005 Up-regulation of functional chemokine receptor CCR3 in human renal cell carcinoma. Clinical cancer research : an official journal of the American Association for Cancer Research 90 15814620
2003 The CCR3 receptor is involved in eosinophil differentiation and is up-regulated by Th2 cytokines in CD34+ progenitor cells. Journal of immunology (Baltimore, Md. : 1950) 83 12496441
2014 Safety and efficacy of an oral CCR3 antagonist in patients with asthma and eosinophilic bronchitis: a randomized, placebo-controlled clinical trial. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology 79 24286456
2010 Eotaxins and CCR3 interaction regulates the Th2 environment of cutaneous T-cell lymphoma. The Journal of investigative dermatology 77 20505746
2022 Molecular insights into ligand recognition and activation of chemokine receptors CCR2 and CCR3. Cell discovery 76 35570218
2006 Eosinophils and CCR3 regulate interleukin-13 transgene-induced pulmonary remodeling. The American journal of pathology 76 17148674
2005 Differential expression of CCR3 and CXCR3 by human lung and bone marrow-derived mast cells: implications for tissue mast cell migration. Journal of leukocyte biology 74 15673545
2004 CCL11 (Eotaxin) induces CCR3-dependent smooth muscle cell migration. Arteriosclerosis, thrombosis, and vascular biology 74 15130922
2003 Eotaxins and CCR3 receptor in inflammatory and allergic skin diseases: therapeutical implications. Current drug targets. Inflammation and allergy 74 14561178
2005 CCR3 expression and function in asthmatic airway smooth muscle cells. Journal of immunology (Baltimore, Md. : 1950) 72 16081847
2000 Characterization of binding between the chemokine eotaxin and peptides derived from the chemokine receptor CCR3. The Journal of biological chemistry 70 10859315
2002 Functional expression of the eotaxin receptor CCR3 in CD30+ cutaneous T-cell lymphoma. Blood 69 12393570
2014 Structural basis of receptor sulfotyrosine recognition by a CC chemokine: the N-terminal region of CCR3 bound to CCL11/eotaxin-1. Structure (London, England : 1993) 66 25450766
1999 CC chemokine receptors, CCR-1 and CCR-3, are potentially involved in antigen-presenting cell function of human peripheral blood monocyte-derived dendritic cells. Blood 66 9864143
2014 Eotaxin-1 promotes prostate cancer cell invasion via activation of the CCR3-ERK pathway and upregulation of MMP-3 expression. Oncology reports 65 24604010
2000 Expression of the chemokine eotaxin and its receptor, CCR3, in human endometrium. Biology of reproduction 65 10642580
2009 High-level production, solubilization and purification of synthetic human GPCR chemokine receptors CCR5, CCR3, CXCR4 and CX3CR1. PloS one 64 19223978
2018 Novel peptide nanoparticle-biased antagonist of CCR3 blocks eosinophil recruitment and airway hyperresponsiveness. The Journal of allergy and clinical immunology 59 29778505
2001 Expression of the chemokine receptor CCR3 on human mast cells. International archives of allergy and immunology 59 11306952
1998 HIV-specific T cell cytotoxicity mediated by RANTES via the chemokine receptor CCR3. The Journal of experimental medicine 55 9687538
2014 Recent progress in the development of antagonists to the chemokine receptors CCR3 and CCR4. Expert opinion on drug discovery 54 24641500
2007 Small molecule receptor agonists and antagonists of CCR3 provide insight into mechanisms of chemokine receptor activation. The Journal of biological chemistry 53 17635911
2002 Expression of a functional eotaxin (CC chemokine ligand 11) receptor CCR3 by human dendritic cells. Journal of immunology (Baltimore, Md. : 1950) 52 12218106
2010 Small molecule antagonists for chemokine CCR3 receptors. Medicinal research reviews 49 19967721
1997 Chemokine receptor CCR3 function is highly dependent on local pH and ionic strength. The Journal of biological chemistry 49 9353270
2004 Up-regulation of CC chemokine, CCL3L1, and receptors, CCR3, CCR5 in human glioblastoma that promotes cell growth. Journal of neuro-oncology 48 15662971
2002 Eotaxin receptor (CCR3) antagonism in asthma and allergic disease. Current drug targets. Inflammation and allergy 48 14561201
2001 CC chemokines and the receptors CCR3 and CCR5 are differentially expressed in the nonneoplastic leukocytic infiltrates of Hodgkin disease. Blood 47 11238088
2013 The chemokine receptor CCR3 participates in tissue remodeling during atopic skin inflammation. Journal of dermatological science 46 23702389
2010 Increased expression of chemokine receptor CCR3 and its ligands in ulcerative colitis: the role of colonic epithelial cells in in vitro studies. Clinical and experimental immunology 46 21077277
2000 CCR3 blockade as a new therapy for asthma. Expert opinion on investigational drugs 45 11060659
2009 CCR3, CCR2A and macrophage inflammatory protein (MIP)-1a, monocyte chemotactic protein-1 (MCP-1) in the mouse hippocampus during and after pilocarpine-induced status epilepticus (PISE) . Neuropathology and applied neurobiology 44 19490431
2005 Discovery of CC chemokine receptor-3 (CCR3) antagonists with picomolar potency. Journal of medicinal chemistry 44 15771462
2011 CCL11-CCR3 interactions promote survival of anaplastic large cell lymphoma cells via ERK1/2 activation. Cancer research 43 21406396
2006 Functional analysis of the chemokine receptor CCR3 on airway epithelial cells. Journal of immunology (Baltimore, Md. : 1950) 43 16920975
2002 Eotaxin and CCR3 are up-regulated in exacerbations of chronic bronchitis. Allergy 42 11991282
2002 Increased expression of eotaxin and its specific receptor CCR3 in bullous pemphigoid. European journal of dermatology : EJD 41 11809592
2001 IL-3 induces down-regulation of CCR3 protein and mRNA in human eosinophils. Journal of immunology (Baltimore, Md. : 1950) 41 11544337
2015 A polymorphism in CCR1/CCR3 is associated with narcolepsy. Brain, behavior, and immunity 40 25986216
2011 CCR3 Blockade Attenuates Eosinophilic Ileitis and Associated Remodeling. The American journal of pathology 40 21945903
2005 Tacrolimus decreases the expression of eotaxin, CCR3, RANTES and interleukin-5 in atopic dermatitis. The British journal of dermatology 38 15948978
2022 Gene knockdown of CCR3 reduces eosinophilic inflammation and the Th2 immune response by inhibiting the PI3K/AKT pathway in allergic rhinitis mice. Scientific reports 37 35354939
2001 Expression pattern of CXCR3, CXCR4, and CCR3 chemokine receptors in the developing human brain. Journal of neuropathology and experimental neurology 37 11202173
2020 Blocking the autocrine regulatory loop of Gankyrin/STAT3/CCL24/CCR3 impairs the progression and pazopanib resistance of clear cell renal cell carcinoma. Cell death & disease 36 32051393
2013 PI3K, ERK, p38 MAPK and integrins regulate CCR3-mediated secretion of mouse and human eosinophil-associated RNases. Allergy 34 23742707
2017 Functional expression of CCL8 and its interaction with chemokine receptor CCR3. BMC immunology 32 29281969
2011 CCR3 and choroidal neovascularization. PloS one 32 21358803
2014 A role for CCL28-CCR3 in T-cell homing to the human upper airway mucosa. Mucosal immunology 31 24917456
2011 Pulmonary epithelial CCR3 promotes LPS-induced lung inflammation by mediating release of IL-8. Journal of cellular physiology 31 21660963
2022 CCL24/CCR3 axis plays a central role in angiotensin II-induced heart failure by stimulating M2 macrophage polarization and fibroblast activation. Cell biology and toxicology 30 36131165
2013 Suppression of laser-induced choroidal neovascularization by a CCR3 antagonist. Investigative ophthalmology & visual science 30 23404125
2006 Increased expression of RANTES, CCR3 and CCR5 in the lesional skin of patients with atopic eczema. International archives of allergy and immunology 29 16449815
2015 Upregulated expression of CCR3 in osteoarthritis and CCR3 mediated activation of fibroblast-like synoviocytes. Cytokine 28 26409848
2005 In vitro and in vivo characterization of a novel CCR3 antagonist, YM-344031. Biochemical and biophysical research communications 27 16343433
2015 Novel CCR3 Antagonists Are Effective Mono- and Combination Inhibitors of Choroidal Neovascular Growth and Vascular Permeability. The American journal of pathology 26 26188133
2007 Genetic effect of CCR3 and IL5RA gene polymorphisms on eosinophilia in asthmatic patients. The Journal of allergy and clinical immunology 26 17983872
2004 Activation of epidermal growth factor receptor via CCR3 in bronchial epithelial cells. Biochemical and biophysical research communications 23 15219825
2021 Cholesterol Is a Dose-Dependent Positive Allosteric Modulator of CCR3 Ligand Affinity and G Protein Coupling. Frontiers in molecular biosciences 22 34490352
2019 CCL26 and CCR3 are associated with the acute inflammatory response in the CNS in experimental autoimmune encephalomyelitis. Journal of neuroimmunology 22 31151084
2017 CCR3 Is Associated with the Death of a Photoreceptor Cell-line Induced by Light Exposure. Frontiers in pharmacology 22 28458639
2023 IgE directly affects eosinophil migration in chronic rhinosinusitis with nasal polyps through CCR3 and predicts the efficacy of omalizumab. The Journal of allergy and clinical immunology 21 37922997
2022 Potent CCR3 Receptor Antagonist, SB328437, Suppresses Colonic Eosinophil Chemotaxis and Inflammation in the Winnie Murine Model of Spontaneous Chronic Colitis. International journal of molecular sciences 21 35887133
2005 A specific CCR3 chemokine receptor antagonist inhibits both early and late phase allergic inflammation in the conjunctiva. Immunologic research 21 16461999
2003 CCR3 expression induced by IL-2 and IL-4 functioning as a death receptor for B cells. Journal of immunology (Baltimore, Md. : 1950) 21 12902471
2000 Cell-type-dependent induction of eotaxin and CCR3 by ionizing radiation. Biochemical and biophysical research communications 21 10708591
2000 The CC chemokine receptor 3 CCR3 is functionally expressed on eosinophils but not on neutrophils. European journal of immunology 21 11069055
2021 Asthma-related inflammation promotes lung metastasis of breast cancer cells through CCL11-CCR3 pathway. Respiratory research 20 33608009
2008 CCR3- and CXCR4-mediated interactions regulate migration of CD34+ human bone marrow progenitors to ischemic myocardium and subsequent tissue repair. The Journal of thoracic and cardiovascular surgery 20 18954648
2003 CCR3 and CXCR3 as drug targets for allergy: principles and potential. Current drug targets. Inflammation and allergy 20 14561176
2000 Receptor reserve analysis of the human CCR3 receptor in eosinophils and CCR3-transfected cells. Journal of leukocyte biology 20 10733106
1999 New variations of human CC-chemokine receptors CCR3 and CCR4. Genes and immunity 20 11196669
2023 Chemokine CCL7 mediates trigeminal neuropathic pain via CCR2/CCR3-ERK pathway in the trigeminal ganglion of mice. Molecular pain 19 36998150
2011 Enhanced CCR5+/CCR3+ T helper cell ratio in patients with active cutaneous lupus erythematosus. Lupus 19 21844117
2023 CCR3 plays a role in murine age-related cognitive changes and T-cell infiltration into the brain. Communications biology 18 36934154
2018 Targeting eotaxin-1 and CCR3 receptor alleviates enteric neuropathy and colonic dysfunction in TNBS-induced colitis in guinea pigs. Neurogastroenterology and motility 18 29968270
2006 Apolipoprotein E deficiency increased microglial activation/CCR3 expression and hippocampal damage in kainic acid exposed mice. Experimental neurology 18 16919271
2010 The function of CCR3 on mouse bone marrow-derived mast cells in vitro. Immunology 17 20050333
2023 Rebalancing liver-infiltrating CCR3+ and CD206+ monocytes improves diet-induced NAFLD. Cell reports 16 37421620

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