Affinage

CCR3

C-C chemokine receptor type 3 · UniProt P51677

Length
355 aa
Mass
41.0 kDa
Annotated
2026-04-28
100 papers in source corpus 42 papers cited in narrative 40 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CCR3 is a Gαi-coupled seven-transmembrane CC chemokine receptor that orchestrates eosinophil recruitment, degranulation, and effector function in allergic inflammation, while also mediating angiogenesis, tissue remodeling, and neurodegeneration in non-hematopoietic contexts. The receptor binds eotaxins (CCL11/CCL24/CCL26), RANTES, MCP-3, MCP-4, and CCL7 via an N-terminal sulfotyrosine-dependent recognition site, triggering pertussis toxin-sensitive Ca²⁺ flux, Src-family kinase (Hck/c-Fgr) recruitment, PI3K–ERK–p38 MAPK activation, and Rac2-dependent actin reorganization that collectively drive chemotaxis, shape change, and eosinophil-associated RNase secretion (PMID:9005985, PMID:10527858, PMID:23742707, PMID:25450766). Beyond leukocytes, CCR3 functions on airway epithelial cells, endothelial cells, smooth muscle cells, fibroblasts, and neurons, where it transactivates EGFR, cross-talks with VEGFR2, and activates CDK5/GSK-3β to promote wound repair, choroidal neovascularization, and tau hyperphosphorylation respectively (PMID:15219825, PMID:21917937, PMID:27878757, PMID:19525930). Receptor activity is allosterically enhanced by membrane cholesterol, regulated transcriptionally by the IKK-2/IκBα/NF-κB pathway, and antagonized by CXCR3 ligands that bind overlapping extracellular-loop epitopes (PMID:34490352, PMID:11694538, PMID:12884299).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1996 High

    Identification of CCR3 as a functional chemokine receptor that also serves as an HIV-1 co-receptor established it as a seven-transmembrane signaling molecule with dual roles in chemokine biology and viral entry.

    Evidence Cell-based infection/fusion assays with CCR3 transfectants co-expressing CD4, ligand competition

    PMID:8674119 PMID:8674120

    Open questions at the time
    • Downstream signaling events upon HIV-1 gp120 engagement of CCR3 undefined
    • Whether CCR3 serves as HIV-1 co-receptor in vivo undetermined
  2. 1997 High

    Demonstration that CCR3 is the dominant receptor mediating eosinophil and Th2 cell chemotaxis to multiple CC chemokines (eotaxin, RANTES, MCP-2/3/4) established its central role in type 2 immune cell trafficking.

    Evidence Antagonistic mAb 7B11, Ca²⁺ flux, radiolabeled binding competition, Th2 isolation and cytokine profiling

    PMID:9005985 PMID:9302298 PMID:9480044

    Open questions at the time
    • Intracellular signaling cascade downstream of CCR3 not yet mapped
    • Relative contribution of each ligand in vivo unknown
  3. 1997 High

    Alanine scanning of RANTES and characterization of CCR3 sensitivity to pH/NaCl defined a two-site chemokine–receptor interaction model and revealed that microenvironmental conditions tune CCR3 ligand affinity.

    Evidence Systematic RANTES mutagenesis with binding/Ca²⁺ assays; ligand binding under varied ionic/pH conditions

    PMID:9289016 PMID:9353270

    Open questions at the time
    • Structural basis for pH sensitivity not determined
    • In vivo relevance of microenvironmental modulation unproven
  4. 1999 Medium

    Discovery that eotaxin-activated CCR3 recruits Src-family kinases Hck and c-Fgr and drives actin reorganization linked receptor engagement to a defined tyrosine kinase signaling axis required for eosinophil chemotaxis.

    Evidence Co-immunoprecipitation of Hck/c-Fgr with CCR3 post-internalization, herbimycin A inhibition, immunofluorescence

    PMID:10527858

    Open questions at the time
    • No reciprocal pull-down or direct binding assay for Hck/c-Fgr–CCR3 interaction
    • Kinase substrates downstream of Hck/c-Fgr not identified
    • Role of receptor internalization in kinase recruitment unclear
  5. 2000 High

    Functional dissection revealed that CCR3 exclusively mediates eosinophil degranulation (EDN release) even though non-CCR3 pathways can trigger Ca²⁺ flux, and NMR mapping identified the CCR3 N-terminal DDYY region and eotaxin N-loop groove as the initial binding interface.

    Evidence CCR3-specific antibody blocking of degranulation vs. Ca²⁺; ¹H-¹⁵N NMR of eotaxin–CCR3 peptide complex

    PMID:10859315 PMID:10984371

    Open questions at the time
    • Full-length receptor–ligand complex structure not solved
    • Structural basis for coupling between binding and degranulation signaling not established
  6. 2001 High

    Extending CCR3 function beyond leukocytes, studies showed it mediates angiogenesis in endothelial cells, signals in airway epithelium, directs mast cell chemotaxis, and is transcriptionally regulated by the IKK-2/IκBα/NF-κB pathway.

    Evidence Chick CAM/Matrigel/aortic ring angiogenesis assays, epithelial Ca²⁺ flux and tyrosine phosphorylation, mast cell migration with anti-CCR3, gain/loss-of-function IKK-2/IκBα mutants and IκBα-KO mice

    PMID:11160184 PMID:11306952 PMID:11390513 PMID:11694538

    Open questions at the time
    • NF-κB binding sites on CCR3 promoter not mapped
    • Relative importance of CCR3 vs. VEGFR signaling in angiogenesis unclear
  7. 2002 High

    CCR3 knockout mice lack eosinophilic inflammation and airway hyperresponsiveness in allergic models, and systematic intracellular-loop mutagenesis defined the DRY motif and all three ICLs as essential for G protein coupling, establishing CCR3 as non-redundant for allergic eosinophilia in vivo.

    Evidence CCR3-KO epicutaneous OVA model; alanine-scanning mutagenesis of 15 ICL triplets with chemotaxis readout

    PMID:11877470 PMID:11920572

    Open questions at the time
    • Other compensatory receptors in chronic settings not evaluated
    • Exact Gα subunit preference at ICL interfaces not biochemically defined
  8. 2005 High

    Genetic epistasis showed eotaxin-1/eotaxin-2 double knockouts phenocopy CCR3 deletion for airway eosinophilia, and CXCL9 was found to inhibit CCR3-mediated Rac2 activation directly through the receptor, establishing a natural antagonist mechanism.

    Evidence Multiple KO combinations in OVA asthma model; Rac2-KO and CCR3-KO eosinophil F-actin and transmigration assays

    PMID:15802529 PMID:16210640

    Open questions at the time
    • Structural basis for CXCR3-ligand antagonism at CCR3 not resolved
    • Role of Rac1 vs. Rac2 in different CCR3-expressing cell types not distinguished
  9. 2009 High

    CCR3 was identified as specifically expressed on choroidal neovascular endothelium in AMD patients, and its blockade inhibited CNV independently of eosinophils/mast cells, establishing a direct pro-angiogenic function.

    Evidence Immunohistochemistry of human AMD tissue, CCR3-KO and pharmacological blockade in laser-induced CNV, endothelial proliferation in eosinophil/mast-cell-deficient mice

    PMID:19525930

    Open questions at the time
    • Which eotaxin drives CNV in human AMD not determined
    • Clinical efficacy of CCR3 blockade in AMD not validated
  10. 2011 High

    CCR3 transphosphorylates and physically associates with VEGFR2 in choroidal endothelial cells, and drives ALCL survival through ERK–Bcl-xL/survivin, revealing receptor cross-talk and pro-survival signaling as additional mechanistic outputs.

    Evidence Co-IP of CCR3–VEGFR2, phospho-VEGFR2/Akt/Rac1 Western blots; ERK inhibitor blockade of ALCL cell survival and in vivo tumor growth

    PMID:21406396 PMID:21917937

    Open questions at the time
    • Whether CCR3–VEGFR2 complex forms in other vascular beds unknown
    • Direct kinase responsible for VEGFR2 transphosphorylation not identified
  11. 2013 Medium

    CCR3-mediated EAR secretion was mapped to a Gαi→PI3K→ERK/p38 MAPK cascade requiring integrin-dependent spreading, and CCL26–CCR3 was shown to drive dermal fibroblast wound repair, expanding the receptor's downstream signaling map and tissue-remodeling roles.

    Evidence Specific signaling inhibitors and integrin-blocking antibodies in primary eosinophils; Ca²⁺/migration/wound-repair assays in dermal fibroblasts

    PMID:23702389 PMID:23742707

    Open questions at the time
    • PI3K isoform specificity not determined
    • Whether integrin requirement reflects co-signaling or physical constraint not resolved
  12. 2014 High

    Crystal structure of the sulfo-CCR3 N-terminal peptide bound to CCL11 revealed that sulfotyrosine residues form specific salt-bridge, hydrophobic, and cation-π contacts with conserved chemokine residues, explaining high-affinity ligand recognition.

    Evidence X-ray crystallography of sulfo-CCR3(8–23)–CCL11 complex, mass spectrometry confirming sulfation, receptor activity assays

    PMID:25450766

    Open questions at the time
    • Full-length CCR3–CCL11 complex structure not solved
    • Contribution of individual sulfotyrosines to in vivo signaling not determined
  13. 2016 High

    CCR3 activation by CCL11 in neurons triggers CDK5/GSK-3β-mediated tau hyperphosphorylation and Aβ production; CCR3 deletion in APP/PS1 mice reduces Alzheimer-related pathology, linking CCR3 to neurodegeneration.

    Evidence CCR3-KO crossed with APP/PS1 transgenic mice, CCR3 antagonist GW766994, Western blots for tau/CDK5/GSK-3β phosphorylation, Aβ ELISA, dendritic spine analysis

    PMID:27878757

    Open questions at the time
    • Source of CCL11 in the AD brain not identified
    • Whether CCR3 blockade is therapeutic after disease onset unknown
  14. 2018 Medium

    A biased CCR3 peptide nanoparticle antagonist (R321) selectively inhibits early G protein-dependent ERK activation while sparing β-arrestin-mediated signaling, promoting receptor degradation and blocking eosinophil recruitment in vivo, demonstrating pharmacologically exploitable signaling bias.

    Evidence NMR peptide binding, ERK phase dissection by Western blot, confocal internalization/degradation, triple-allergen mouse asthma model

    PMID:29778505

    Open questions at the time
    • β-arrestin pathway contributions to CCR3 biology in vivo not resolved
    • Single study; biased agonism not independently confirmed
  15. 2021 High

    Reconstitution of purified CCR3 in defined lipid environments demonstrated that cholesterol is a dose-dependent positive allosteric modulator, directly enhancing both CCL11 binding affinity and Gαi3 GTPase activity.

    Evidence Purified E. coli-expressed CCR3 in SMALPs and proteoliposomes with titrated cholesterol, GTPase activity assay

    PMID:34490352

    Open questions at the time
    • Cholesterol binding site on CCR3 not structurally identified
    • Physiological range of membrane cholesterol variation in eosinophils not characterized
  16. 2022 High

    Cryo-EM structure of apo CCR3 revealed that ICL2 interactions with Gα are more critical than ICL3 for G protein activation and provided structural basis for constitutive receptor activity, completing the structural picture of CCR3–G protein coupling.

    Evidence Cryo-EM structure determination with complementary G protein coupling functional assays

    PMID:35570218

    Open questions at the time
    • Ligand-bound active-state cryo-EM structure not yet solved
    • Structural basis for biased signaling (G protein vs. β-arrestin) not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • A complete structural understanding of CCR3 activation—including a full-length CCR3–chemokine–Gi ternary complex structure, the molecular basis for β-arrestin-biased signaling, and the cholesterol binding site—remains to be determined.
  • No ternary complex structure of full-length CCR3–ligand–Gi
  • Molecular basis of β-arrestin-biased vs. G protein-biased signaling unknown
  • In vivo therapeutic efficacy of CCR3-targeted agents in AMD and neurodegeneration not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 6 GO:0098772 molecular function regulator activity 3
Localization
GO:0005886 plasma membrane 8
Pathway
R-HSA-162582 Signal Transduction 11 R-HSA-168256 Immune System 10
Partners
CCL11CCL24CCL26CCL5FGRHCKRAC2VEGFR2

Evidence

Reading pass · 40 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 (fusion cofactor) for a restricted subset of primary HIV-1 isolates; binding of the CCR3 ligand eotaxin blocks this infection, and utilization depends on the V3 region of HIV-1 gp120. Cell-based infection/fusion assay with CCR3 transfectants, co-expression of CD4 and CCR3, chemokine inhibition experiments Cell High 8674119 8674120
1997 CCR3 is selectively expressed on human Th2 cells; eotaxin stimulation through CCR3 induces intracellular calcium increases and chemotaxis of CCR3+ T cells, and these cells produce IL-4 and IL-5. Anti-CCR3 antibody-based cell isolation, intracellular Ca2+ flux assay, chemotaxis assay, cytokine production measurement Science High 9302298 9480044
1997 CCR3 mediates eosinophil responses (chemotaxis and calcium flux) to multiple CC chemokines including eotaxin, RANTES, MCP-2, MCP-3, and MCP-4; a selective antagonistic monoclonal antibody (7B11) blocks >95% of these responses. Radiolabeled chemokine binding competition assay, calcium flux assay, chemotaxis assay with antagonistic mAb 7B11 The Journal of clinical investigation High 9005985
1997 Alanine scanning mutagenesis of RANTES identified distinct but overlapping binding epitopes for CCR3 (F12 in N-loop), CCR1 (R17), and CCR5 (F12, I15, P2); residues P2 and Y3 near the RANTES N-terminus are required for CCR3 signal transduction, defining a two-site model of chemokine-receptor interaction. Alanine scanning mutagenesis of RANTES, receptor binding assays, calcium mobilization assays Biochemistry High 9289016
1997 CCR3 function is highly sensitive to extracellular pH and NaCl concentration; small physiological variations dramatically alter eotaxin binding, CCR3-mediated Ca2+ mobilization, and eosinophil migration, suggesting the tissue microenvironment modulates CCR3 affinity. Radiolabeled ligand binding assay, intracellular Ca2+ mobilization assay, eosinophil migration assay under varied pH and salt conditions The Journal of biological chemistry Medium 9353270
1998 CCR3 (but not CCR5) is the essential co-receptor for microglia HIV-1 infection among CCR3/CCR5-expressing cells; antibodies to CCR5 but not CCR3 prevented monocyte infection, establishing differential receptor usage in mononuclear phagocyte subsets. Antibody blockade of CCR3 and CCR5, infection of purified monocyte and microglia populations with macrophage-tropic HIV-1 strains Journal of virology Medium 9525662
1998 IFN-γ upregulates CCR3 (along with CCR1 and CCR5) surface expression and mRNA in monocytoid U937 cells, resulting in enhanced Ca2+ mobilization, chemotaxis, and increased HIV-1 entry. Flow cytometry, mRNA expression, Ca2+ mobilization, cell migration assays, HIV-1 entry assay in IFN-γ-treated U937 cells Blood Medium 9616137
1998 RANTES enhances HIV-1-specific CTL killing via CCR3; the effect is blocked by a CCR3-specific antibody and by pertussis toxin, indicating G protein-coupled CCR3 signaling mediates this cytotoxic enhancement. MCP-3, MCP-4, and eotaxin also enhance lysis through CCR3, while CCR1, CCR2, CCR5, and CXCR4 ligands are inactive. CTL killing assay with specific antibody blockade, pertussis toxin treatment, chemokine panel testing The Journal of experimental medicine Medium 9687538
1999 Eotaxin stimulation through CCR3 induces tyrosine phosphorylation of multiple cellular proteins in eosinophils, recruits Src family kinases Hck and c-Fgr to CCR3 after receptor internalization, and causes actin reorganization; herbimycin A (tyrosine kinase inhibitor) blocks both phosphorylation and chemotaxis. Co-immunoprecipitation, immunofluorescence microscopy, tyrosine kinase inhibitor treatment, chemotaxis assay Biochemical and biophysical research communications Medium 10527858
1999 CCR3 mediates eosinophil shape change in response to eotaxin, eotaxin-2, MCP-4, and RANTES; MIP-1α induces eosinophil responses through a non-CCR3 pathway (likely CCR1); pre-incubation without extracellular Ca2+ upregulates non-CCR3 signaling pathways. Gated autofluorescence/forward scatter assay for leukocyte shape change, antibody blocking of CCR3 Journal of immunology Medium 10072545
2000 CCR3 chemokine-induced eosinophil degranulation (release of eosinophil-derived neurotoxin) is mediated exclusively through CCR3; although non-CCR3 ligands (e.g., MCP-1) induce Ca2+ flux, only CCR3 ligands (MCP-3, MCP-4, RANTES, eotaxin) induce degranulation; IL-5 priming enhances CCR3-dependent but not non-CCR3 degranulation. Ca2+ flux assay, RIA for eosinophil-derived neurotoxin, CCR3-specific antibody blocking, IL-5 priming The Journal of allergy and clinical immunology Medium 10984371
2000 The N-terminal peptide of CCR3 (residues 1–35 and 8–23) binds eotaxin with low affinity (Kd ~80–136 µM); NMR spectroscopy identified the N-loop/β2-β3 hairpin groove of eotaxin as the binding surface; the central DDYY region of the CCR3 N-terminus is involved in the interaction. Synthetic peptide binding assay, 1H-15N NMR spectroscopy, 15N-filtered TOCSY The Journal of biological chemistry High 10859315
2000 CCR3 signaling in eosinophilic AML14.3D10 cells does not inhibit adenylate cyclase (unlike most GPCRs), uses pertussis toxin-sensitive Ca2+ transients inhibited by PMA but not forskolin, and eotaxin stimulation causes rapid and prolonged receptor internalization without degradation. cAMP assay, Ca2+ flux assay, pertussis toxin and PMA treatment, receptor internalization/degradation assays, CCR3 promoter-luciferase reporter Journal of immunology Medium 10623856
2000 CCL11 (eotaxin) binds with high affinity to CXCR3, which can act as a decoy receptor sequestering CCL11; CXCR3 ligands (CXCL9, CXCL10, CXCL11) inhibit CCR3-mediated eosinophil responses by acting as CCR3 antagonists; CCR3-CCR1 chimeric receptor analysis revealed that CCL11 and CXCL11 share overlapping binding sites in the CCR3 extracellular loops. Binding assays, chemotaxis assay, Ca2+ flux, CCR3-CCR1 chimeric receptor construction and analysis European journal of immunology Medium 12884299
2001 CCR3 is expressed on human airway epithelial cells and is functional: eotaxin stimulation induces intracellular Ca2+ flux and tyrosine phosphorylation, blocked by anti-CCR3 mAb (7B11) or pertussis toxin; 125I-eotaxin binding confirmed expected ligand specificity. Northern blot, Western blot, flow cytometry, Ca2+ flux assay, tyrosine phosphorylation assay, 125I-eotaxin binding assay, mAb blockade, pertussis toxin treatment Journal of immunology High 11160184
2001 CCR3 expressed on human mast cells mediates chemotaxis in response to eotaxin and RANTES; pre-incubation with anti-CCR3 antibody abrogates eotaxin-induced mast cell migration, but eotaxin does not induce histamine release from lung mast cells. Immunohistochemistry, flow cytometry, chemotaxis assay with anti-CCR3 antibody blockade, histamine release assay International archives of allergy and immunology Medium 11306952
2001 CCL11 (eotaxin) promotes angiogenesis via CCR3 expressed on human microvascular endothelial cells; CCL11-induced endothelial chemotaxis was inhibited by antibodies to CCL11 or CCR3; in vivo angiogenesis (chick CAM and Matrigel assays) was confirmed, and rat aortic sprouting assay showed the response is direct (not eosinophil-mediated). Endothelial chemotaxis assay with antibody blockade, chick chorioallantoic membrane assay, Matrigel plug assay, rat aortic sprouting assay Journal of immunology High 11390513
2001 The IKK-2/IκBα/NF-κB pathway regulates CCR3 expression in fibroblasts: transdominant IκBα mutant blocks TNF-α-induced CCR3 expression, and constitutively active IKK-2 drives CCR3 expression without TNF-α; IκBα-deficient mice show elevated CCR3 in skin associated with dermatitis. Stable transfection of IκBα and IKK-2 mutants, luciferase reporter assay, immunohistochemistry in knockout mice, RT-PCR The Journal of biological chemistry High 11694538
2002 Alanine scanning mutagenesis of CCR3's three intracellular loops revealed all three are required for G protein coupling and chemotactic function; in ICL2, the DRY motif residues D130 and R131 require acidic/basic character for function; Y132 is critical for surface expression and chemotaxis. Site-directed alanine triplet and point mutagenesis, flow cytometry for surface expression, chemotaxis assay European journal of immunology High 11920572
2002 CCR3 is essential for skin and lung eosinophilia and airway hyperresponsiveness in a murine model of epicutaneous OVA sensitization; CCR3-/- mice lack skin and lung eosinophils and fail to develop AHR despite normal IgE, Th2 cytokines (IL-4/IL-5), and mast cell numbers. CCR3 knockout mouse model, epicutaneous OVA sensitization, histology, BAL cell counts, AHR measurement, cytokine quantification The Journal of clinical investigation High 11877470
2002 IL-16 activates eosinophils via CD4 receptor to release preformed RANTES, which then autocrinally signals through CCR3 to stimulate LTC4 production and preferential IL-4 (not IL-12) release; CCR3 inhibitors (Met-RANTES, anti-CCR3 mAb) and neutralizing anti-eotaxin/anti-RANTES antibodies block these effects. LTC4 and cytokine RIA, antibody blockade (anti-CD4, anti-CCR3, anti-RANTES, anti-eotaxin), pertussis toxin, Met-RANTES antagonism, brefeldin A treatment Journal of immunology High 11971026
2003 Eotaxin induces Ca2+ mobilization and chemotaxis in CD34+ cord blood progenitor cells via CCR3, and directly drives eosinophil differentiation from CD34+ progenitors; Th2 cytokines (IL-4, IL-13) upregulate CCR3 on progenitors while IL-12/IFN-γ decrease it; this differentiation is IL-3-, IL-5-, and GM-CSF-independent. In situ RT-PCR, immunostaining, flow cytometry, Ca2+ mobilization assay, in vitro differentiation assay with neutralizing antibodies Journal of immunology Medium 12496441
2004 CCL11 (eotaxin) induces vascular smooth muscle cell (SMC) migration via CCR3; CCR3 mRNA and protein are present in mouse aortic SMCs; migration is inhibited by anti-CCR3 but not anti-CCR2 antibody; CCR3 and CCL11 are upregulated in SMCs after arterial injury. RT-PCR, Western blot, flow cytometry, Boyden chamber chemotaxis, scrape-wound assay with specific antibody blockade, in vivo arterial injury model Arteriosclerosis, thrombosis, and vascular biology High 15130922
2004 CCR3 in bronchial epithelial cells transactivates the epidermal growth factor receptor (EGFR) upon eotaxin stimulation; EGFR tyrosine phosphorylation is dose-dependent; EGFR inhibitor AG1478 blocks CCR3-induced MAP kinase phosphorylation and IL-8 production. Western blot for EGFR phosphorylation, EGFR inhibitor (AG1478) treatment, ELISA for IL-8 in bronchial epithelial cells Biochemical and biophysical research communications Medium 15219825
2005 Eotaxin-2 has a dominant role in airway (luminal) eosinophilia in allergen-induced asthma; combined deletion of eotaxin-1 and eotaxin-2 (DKO) and CCR3 deletion both markedly reduce tissue eosinophilia, abolish organized peribronchial/perivascular eosinophil accumulation, and eotaxin-2 is expressed by macrophages in BAL fluid. Genetic deletion (eotaxin-1 KO, eotaxin-2 KO, eotaxin-1/2 DKO, CCR3 KO), OVA-induced asthma model, BAL and tissue eosinophil counts Journal of immunology High 16210640
2005 CXCL9 (Mig) inhibits eosinophil chemoattraction and F-actin formation through a CCR3-dependent mechanism by blocking eotaxin-induced Rac GTPase activation; Rac2-deficient eosinophils show impaired transmigration and actin polymerization, and CXCL9 cannot inhibit responses in CCR3-deficient eosinophils, establishing CCR3 as the mediator of this inhibitory signal. CCR3 and Rac2 gene-targeted eosinophils, F-actin formation assay, Rac GTPase activation assay, transmigration assay Blood High 15802529
2006 Oligodendrocyte precursor cells (OPCs) express functional CCR3; CCL11 stimulation induces intracellular Ca2+ rise and concentration-specific effects: increased proliferation, inhibition of migration, and augmentation of differentiation in primary OPCs. RT-PCR, immunofluorescence, Ca2+ mobilization assay, proliferation, migration, and differentiation assays in primary rat OPCs Journal of neuroimmunology Medium 16828880
2006 CCR3 on airway epithelial cells mediates wound repair, cell proliferation, and chemotaxis in response to CCL24 (eotaxin-2), with comparable potency to EGF; CCL11 induces upregulation of profibrogenic genes (FGF-1, FGF-5) and CC/CXC chemokines; a selective CCR3 antagonist inhibits these responses. In vitro wound model, fluorometric proliferation and chemotaxis assays, pathway-specific gene arrays, CCR3 antagonist blockade, immunostaining of bronchial biopsies Journal of immunology High 16920975
2009 CCR3 is specifically expressed on choroidal neovascular endothelial cells in AMD patients; genetic or pharmacological targeting of CCR3 or its eotaxin ligands inhibits injury-induced CNV in mice; CNV suppression by CCR3 blockade is due to direct inhibition of endothelial cell proliferation, is uncoupled from inflammation, and occurs in mice lacking eosinophils or mast cells. Immunohistochemistry, CCR3 genetic knockout/pharmacological blockade, laser-induced CNV mouse model, in vitro endothelial cell proliferation assay in mice lacking eosinophils/mast cells, quantum dot in vivo imaging Nature High 19525930
2011 Activated CCR3 promotes choroidal endothelial cell (CEC) migration and Rac1 activation; ligand-activated CCR3 causes transphosphorylation and co-immunoprecipitation of VEGFR2 with CCR3, demonstrating cross-talk between CCR3 and VEGF signaling pathways; CCR3 inhibitor prevents VEGF-induced CEC migration and Rac1 activation. CCL11-stimulated CEC migration assay, Rac1 activity assay, phospho-Akt and phospho-VEGFR2 Western blot, co-immunoprecipitation of CCR3 and VEGFR2, CCR3 inhibitor treatment Investigative ophthalmology & visual science High 21917937
2011 CCL11 promotes survival of anaplastic large cell lymphoma cells via CCR3-mediated ERK1/2 phosphorylation, inducing anti-apoptotic proteins Bcl-xL and survivin; ERK phosphorylation inhibition completely blocks CCL11-mediated cell survival; autocrine CCL11-CCR3 signaling drives tumor growth in vivo. Cell viability assay, Western blot for ERK1/2 phosphorylation and Bcl-xL/survivin, ERK inhibitor treatment, in vivo tumor growth in CCR3+ cell lines Cancer research Medium 21406396
2013 CCR3 on human dermal fibroblasts mediates intracellular Ca2+ mobilization, enhanced fibroblast migration, and wound repair capacity in response to CCL26 (eotaxin-3); CCL26 is specifically upregulated in atopic (vs. psoriatic) skin by IL-4 and IL-13, implicating CCR3-mediated CCL26-fibroblast signaling in atopic skin tissue remodeling. Flow cytometry, immunofluorescence, Ca2+ mobilization assay, cell proliferation, migration, and repair capacity assays in dermal fibroblasts Journal of dermatological science Medium 23702389
2013 CCR3-mediated secretion of eosinophil-associated RNases (EARs) requires activation of PI3K, ERK, and p38 MAPK, and is Gαi-dependent; β1 and β2 integrins are essential for EAR secretion, and spreading is obligatory for secretion in both mouse and human eosinophils. RNase activity assay, specific signaling inhibitors for PI3K/ERK/p38 MAPK, integrin blocking antibodies, pertussis toxin, adhesion microscopy in primary mouse and human eosinophils Allergy Medium 23742707
2014 Sulfotyrosine residues in the N-terminal region (residues 8–23) of CCR3 dramatically enhance binding to CCL11/eotaxin-1; crystal structure of CCL11 bound to sulfo-CCR3(8–23) peptide reveals sulfotyrosine residues form hydrophobic, salt bridge, and cation-π interactions with conserved CC chemokine residues; intact CCR3 is sulfated in cells and sulfation enhances receptor activity. X-ray crystallography (NMR structure of peptide-chemokine complex), sulfopeptide binding assays, receptor activity assays, mass spectrometry for sulfation Structure High 25450766
2016 CCL11 (CCR3 ligand) activates CDK5 and GSK-3β via CCR3, leading to tau hyperphosphorylation, Aβ production, and dendritic spine loss in hippocampal neurons; CCR3 deletion in APP/PS1 mice significantly reduces CDK5/GSK-3β phosphorylation, tau hyperphosphorylation, Aβ deposition, and synaptic loss; all CCL11 effects are blocked by CCR3 antagonist GW766994. Primary hippocampal neuronal culture, Western blot for CDK5/GSK-3β/tau phosphorylation, Aβ ELISA, dendritic spine analysis, CCR3 KO in AD transgenic mice, CCR3 antagonist treatment Molecular neurobiology High 27878757
2016 CCL7-CCR3 interaction in colon cancer cells promotes cellular proliferation, invasion, and migration via ERK and JNK signaling pathways; CCL7-overexpressing cells form faster-growing tumors and develop liver/lung metastases in orthotopic mouse models. CCL7-overexpressing HCT116/HT29 cell lines, in vitro proliferation/invasion/migration assays, ERK/JNK Western blots, ectopic and orthotopic mouse tumor models Oncotarget Medium 27167205
2018 A biased CCR3 peptide nanoparticle antagonist (R321) inhibits only the early phase of ERK1/2 activation (not the late β-arrestin-associated phase), promotes CCR3 internalization and degradation, and effectively blocks eosinophil recruitment and airway hyperresponsiveness in a mouse asthma model. Dynamic light scattering, NMR peptide binding, flow cytometry, confocal microscopy, Western blot for ERK1/2 phases, in vivo triple-allergen mouse asthma model The Journal of allergy and clinical immunology Medium 29778505
2021 Cholesterol acts as a dose-dependent positive allosteric modulator of CCR3: increasing cholesterol concentration enhances CCR3 affinity for CCL11 in both SMALPs and proteoliposomes, and this heightened receptor activation directly increases GTPase activity of the bound Gαi3 subunit. In vitro CCR3 reconstitution in SMALPs and proteoliposomes, ligand binding assay, GTPase activity assay with purified E. coli-expressed CCR3 Frontiers in molecular biosciences High 34490352
2022 Cryo-EM structure of CCR3 in the apo state and functional analysis show that interactions around intracellular loop 2 (ICL2) are conserved and play a more critical role in G-protein activation than ICL3 interactions; extensive hydrophobic and polar interactions between CCR3 and Gα contribute to constitutive receptor activity. Cryo-electron microscopy structure determination, complementary functional experiments (G protein coupling assays) Cell discovery High 35570218
2022 The CCL24/CCR3 axis promotes cardiac fibroblast activation and M2 macrophage polarization; CCR3 is expressed on cardiac macrophages and fibroblasts; CCL24 promotes primary cardiac fibroblast activation through its G protein-coupled receptor function; CCL24 antibody treatment prevents Ang II-induced cardiac hypertrophy and fibrosis. Immunofluorescence co-localization, RNA-seq, CyTOF single-cell analysis, in vitro fibroblast activation assay, in vivo Ang II heart failure model with CCL24 antibody Cell biology and toxicology Medium 36131165

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 2053 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 Chemokine receptor usage by human eosinophils. The importance of CCR3 demonstrated using an antagonistic monoclonal antibody. The Journal of clinical investigation 357 9005985
2000 A novel chemokine ligand for CCR10 and CCR3 expressed by epithelial cells in mucosal tissues. Journal of immunology (Baltimore, Md. : 1950) 242 10975800
1997 Functional expression of the eotaxin receptor CCR3 in T lymphocytes co-localizing with eosinophils. Current biology : CB 218 9480044
2002 CCR3 is essential for skin eosinophilia and airway hyperresponsiveness in a murine model of allergic skin inflammation. The Journal of clinical investigation 213 11877470
2001 Eotaxin (CCL11) induces in vivo angiogenic responses by human CCR3+ endothelial cells. Journal of immunology (Baltimore, Md. : 1950) 208 11390513
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) 189 16210640
2000 Expression of the beta-chemokine receptors CCR2, CCR3 and CCR5 in multiple sclerosis central nervous system tissue. Journal of neuroimmunology 161 10900353
1999 Differential regulation of eosinophil chemokine signaling via CCR3 and non-CCR3 pathways. Journal of immunology (Baltimore, Md. : 1950) 152 10072545
1999 Enhanced expression of eotaxin and CCR3 in atopic dermatitis. The Journal of investigative dermatology 152 10417617
1997 Distinct but overlapping epitopes for the interaction of a CC-chemokine with CCR1, CCR3 and CCR5. Biochemistry 149 9289016
1998 Role of the beta-chemokine receptors CCR3 and CCR5 in human immunodeficiency virus type 1 infection of monocytes and microglia. Journal of virology 131 9525662
2008 Antisense therapy against CCR3 and the common beta chain attenuates allergen-induced eosinophilic responses. American journal of respiratory and critical care medicine 116 18244953
2001 Interleukin-5 induces CD34(+) eosinophil progenitor mobilization and eosinophil CCR3 expression in asthma. American journal of respiratory and critical care medicine 109 11704586
2000 Chemokines induce eosinophil degranulation through CCR-3. The Journal of allergy and clinical immunology 108 10984371
2003 CCR3 functional responses are regulated by both CXCR3 and its ligands CXCL9, CXCL10 and CXCL11. European journal of immunology 106 12884299
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
1999 Depletion of eosinophils in mice through the use of antibodies specific for C-C chemokine receptor 3 (CCR3). Journal of leukocyte biology 83 10380909
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 78 24286456
2010 Eotaxins and CCR3 interaction regulates the Th2 environment of cutaneous T-cell lymphoma. The Journal of investigative dermatology 76 20505746
2006 Eosinophils and CCR3 regulate interleukin-13 transgene-induced pulmonary remodeling. The American journal of pathology 76 17148674
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
2022 Molecular insights into ligand recognition and activation of chemokine receptors CCR2 and CCR3. Cell discovery 72 35570218
2011 Robust expression of CCR3 as a single basophil selection marker in flow cytometry. Allergy 72 20608915
1998 Interferon-gamma increases expression of chemokine receptors CCR1, CCR3, and CCR5, but not CXCR4 in monocytoid U937 cells. Blood 72 9616137
2000 Characterization of binding between the chemokine eotaxin and peptides derived from the chemokine receptor CCR3. The Journal of biological chemistry 70 10859315
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
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
2002 IL-16 promotes leukotriene C(4) and IL-4 release from human eosinophils via CD4- and autocrine CCR3-chemokine-mediated signaling. Journal of immunology (Baltimore, Md. : 1950) 58 11971026
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
2001 The IKK-2/Ikappa Balpha /NF-kappa B pathway plays a key role in the regulation of CCR3 and eotaxin-1 in fibroblasts. A critical link to dermatitis in Ikappa Balpha -deficient mice. The Journal of biological chemistry 53 11694538
2006 Rosmarinic acid as a downstream inhibitor of IKK-beta in TNF-alpha-induced upregulation of CCL11 and CCR3. British journal of pharmacology 51 16604092
1997 Chemokine receptor CCR3 function is highly dependent on local pH and ionic strength. The Journal of biological chemistry 49 9353270
2016 Hypoxia induced CCL28 promotes angiogenesis in lung adenocarcinoma by targeting CCR3 on endothelial cells. Scientific reports 48 27250766
2016 Targeting CCR3 to Reduce Amyloid-β Production, Tau Hyperphosphorylation, and Synaptic Loss in a Mouse Model of Alzheimer's Disease. Molecular neurobiology 48 27878757
2010 Small molecule antagonists for chemokine CCR3 receptors. Medicinal research reviews 48 19967721
2002 Eotaxin receptor (CCR3) antagonism in asthma and allergic disease. Current drug targets. Inflammation and allergy 48 14561201
2011 Upregulation of CCR3 by age-related stresses promotes choroidal endothelial cell migration via VEGF-dependent and -independent signaling. Investigative ophthalmology & visual science 45 21917937
2013 The chemokine receptor CCR3 participates in tissue remodeling during atopic skin inflammation. Journal of dermatological science 44 23702389
2006 Functional analysis of the chemokine receptor CCR3 on airway epithelial cells. Journal of immunology (Baltimore, Md. : 1950) 43 16920975
2011 CCL11-CCR3 interactions promote survival of anaplastic large cell lymphoma cells via ERK1/2 activation. Cancer research 42 21406396
2002 Eotaxin and CCR3 are up-regulated in exacerbations of chronic bronchitis. Allergy 42 11991282
2001 Discovery of a novel CCR3 selective antagonist. Bioorganic & medicinal chemistry letters 42 11354381
2011 CCR3 Blockade Attenuates Eosinophilic Ileitis and Associated Remodeling. The American journal of pathology 40 21945903
1999 Novel association of the src family kinases, hck and c-fgr, with CCR3 receptor stimulation: A possible mechanism for eotaxin-induced human eosinophil chemotaxis. Biochemical and biophysical research communications 40 10527858
2017 Stimulation of oral fibroblast chemokine receptors identifies CCR3 and CCR4 as potential wound healing targets. Journal of cellular physiology 39 28387445
2017 CCR3 Monoclonal Antibody Inhibits Eosinophilic Inflammation and Mucosal Injury in a Mouse Model of Eosinophilic Gastroenteritis. Allergy, asthma & immunology research 39 28497923
2015 A polymorphism in CCR1/CCR3 is associated with narcolepsy. Brain, behavior, and immunity 39 25986216
2018 Interleukin-4 activated macrophages mediate immunity to filarial helminth infection by sustaining CCR3-dependent eosinophilia. PLoS pathogens 38 29547639
2005 Tacrolimus decreases the expression of eotaxin, CCR3, RANTES and interleukin-5 in atopic dermatitis. The British journal of dermatology 37 15948978
2001 Expression pattern of CXCR3, CXCR4, and CCR3 chemokine receptors in the developing human brain. Journal of neuropathology and experimental neurology 37 11202173
2006 CCR3 monoclonal antibody inhibits airway eosinophilic inflammation and mucus overproduction in a mouse model of asthma. Acta pharmacologica Sinica 36 17112414
2013 PI3K, ERK, p38 MAPK and integrins regulate CCR3-mediated secretion of mouse and human eosinophil-associated RNases. Allergy 34 23742707
2002 Alanine scanning mutagenesis of CCR3 reveals that the three intracellular loops are essential for functional receptor expression. European journal of immunology 34 11920572
2007 Selective suppression of Th2-mediated airway eosinophil infiltration by low-molecular weight CCR3 antagonists. International immunology 33 17804691
2006 Recent developments in CCR3 antagonists. Current opinion in drug discovery & development 33 16889234
2000 Molecular analysis of CCR-3 events in eosinophilic cells. Journal of immunology (Baltimore, Md. : 1950) 33 10623856
2021 Stromal CCL5 Promotes Breast Cancer Progression by Interacting with CCR3 in Tumor Cells. International journal of molecular sciences 32 33671956
2005 CXCL9 inhibits eosinophil responses by a CCR3- and Rac2-dependent mechanism. Blood 32 15802529
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
2010 Local proliferation and mobilization of CCR3(+)  CD34(+) eosinophil-lineage-committed cells in the lung. Immunology 31 20875077
2001 The presence of chemokine receptor (CCR5, CXCR3, CCR3)-positive cells and chemokine (MCP1, MIP-1alpha, MIP-1beta, IP-10)-positive cells in human periapical granulomas. Cytokine 31 11683586
2000 Comparison of the structure of vMIP-II with eotaxin-1, RANTES, and MCP-3 suggests a unique mechanism for CCR3 activation. Biochemistry 31 11041848
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 28 16449815
2009 Ablation of type I hypersensitivity in experimental allergic conjunctivitis by eotaxin-1/CCR3 blockade. International immunology 27 19147836
2005 In vitro and in vivo characterization of a novel CCR3 antagonist, YM-344031. Biochemical and biophysical research communications 27 16343433
2007 Genetic effect of CCR3 and IL5RA gene polymorphisms on eosinophilia in asthmatic patients. The Journal of allergy and clinical immunology 26 17983872
2015 Novel CCR3 Antagonists Are Effective Mono- and Combination Inhibitors of Choroidal Neovascular Growth and Vascular Permeability. The American journal of pathology 25 26188133
2006 Oligodendrocyte precursor cells express a functional chemokine receptor CCR3: implications for myelination. Journal of neuroimmunology 23 16828880
2004 Activation of epidermal growth factor receptor via CCR3 in bronchial epithelial cells. Biochemical and biophysical research communications 23 15219825
2004 CD4+ CCR5+ and CD4+ CCR3+ lymphocyte subset and monocyte apoptosis in patients with acute visceral leishmaniasis. Immunology 23 15379987
1999 CD4 receptor-dependent entry of human immunodeficiency virus type-1 env-pseudotypes into CCR5-, CCR3-, and CXCR4-expressing human alveolar macrophages is preferentially mediated by the CCR5 coreceptor. American journal of respiratory cell and molecular biology 23 10226056
2021 Cholesterol Is a Dose-Dependent Positive Allosteric Modulator of CCR3 Ligand Affinity and G Protein Coupling. Frontiers in molecular biosciences 22 34490352
2017 CCR3 Is Associated with the Death of a Photoreceptor Cell-line Induced by Light Exposure. Frontiers in pharmacology 22 28458639
2004 The Th2 response as monitored by CRTH2 or CCR3 expression is severely decreased during septic shock. Clinical immunology (Orlando, Fla.) 22 15507393
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
2019 CCL26 and CCR3 are associated with the acute inflammatory response in the CNS in experimental autoimmune encephalomyelitis. Journal of neuroimmunology 21 31151084
2005 A specific CCR3 chemokine receptor antagonist inhibits both early and late phase allergic inflammation in the conjunctiva. Immunologic research 21 16461999
2000 Cell-type-dependent induction of eotaxin and CCR3 by ionizing radiation. Biochemical and biophysical research communications 21 10708591
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 20 35887133
2021 Asthma-related inflammation promotes lung metastasis of breast cancer cells through CCL11-CCR3 pathway. Respiratory research 20 33608009
2021 The Chemokine Receptor CCR3 Is Potentially Involved in the Homing of Prostate Cancer Cells to Bone: Implication of Bone-Marrow Adipocytes. International journal of molecular sciences 20 33671469
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
1999 New variations of human CC-chemokine receptors CCR3 and CCR4. Genes and immunity 20 11196669