CCR3 (C-C Chemokine Receptor Type 3) <table class="infobox infobox-gene">Gene Symbol </td>Full Name </td>Aliases </td>Chromosomal Location </td>NCBI Gene ID </td>OMIM </td>Ensembl ID </td>UniProt ID </td>Protein Length </td>Molecular Weight </td>CCL11 (Eotaxin-1) </td>CCL24 (Eotaxin-2) </td>CCL26 (Eotaxin-3) </td>CCL5 (RANTES) </td>
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CCR3 (C-C Chemokine Receptor Type 3) <table class="infobox infobox-gene">Gene Symbol </td>Full Name </td>Aliases </td>Chromosomal Location </td>NCBI Gene ID </td>OMIM </td>Ensembl ID </td>UniProt ID </td>Protein Length </td>Molecular Weight </td>CCL11 (Eotaxin-1) </td>CCL24 (Eotaxin-2) </td>CCL26 (Eotaxin-3) </td>CCL5 (RANTES) </td>CCL7 (MCP-3) </td>Carboxamides </td>Small Molecule Inhibitors </td>Monoclonal Antibodies </td>
Overview CCR3 (C-C Chemokine Receptor Type 3), also known as CD193, is a G protein-coupled receptor (GPCR) that serves as the primary receptor for eotaxin family chemokines (CCL11, CCL24, CCL26) and other CC chemokines including RANTES (CCL5) and MCP-3 (CCL7)[@damico2009]. Originally characterized for its critical role in eosinophil recruitment during allergic inflammation, emerging research has revealed that CCR3 is also expressed in the central nervous system (CNS) on astrocytes and microglia, where it contributes to neuroinflammatory processes in neurodegenerative diseases[@furuya2013].
Molecular Function
Ligand Binding CCR3 binds multiple chemokines with varying affinities:
Signal Transduction Upon ligand binding, CCR3 triggers intracellular signaling through Gαi proteins:
Gαi Pathway : Inhibits adenylate cyclase, reduces cAMPPI3K Pathway : Activates Akt, promotes cell survivalMAPK Pathway : ERK1/2 activation, cell proliferationPLC Pathway : IP3/DAG production, calcium mobilization
Receptor Trafficking
Constitutive Internalization : Receptor recycles via endosomesDesensitization : GRK-mediated phosphorylation leads to β-arrestin recruitmentRe-sensitization : Receptor returns to cell surfaceExpression Pattern
Immune Cell Expression
Eosinophils : Highest expression; CCR3 is the defining markerTh2 Lymphocytes : Moderate expressionBasophils : Low to moderate expressionMast Cells : Variable expressionPlasmacytoid Dendritic Cells : Lower expressionCNS Expression In the central nervous system, CCR3 is expressed on:
Astrocytes : Particularly reactive astrocytes in neuroinflammatory conditionsMicroglia : Activated microglia express CCR3Endothelial Cells : Brain vasculature expresses CCR3Neurons : Low baseline expression, may increase in diseaseExpression in Disease States
Role in Neurodegeneration
Alzheimer's Disease CCR3 plays a significant role in AD pathophysiology:
Eosinophil Infiltration : CCR3+ eosinophils can infiltrate AD brain parenchymaEotaxin-CCR3 Axis : CCL11/eotaxin is elevated in AD brains and correlates with disease progressionNeuroinflammation : CCR3 signaling on astrocytes and microglia promotes pro-inflammatory cytokine releaseAmyloid Interaction : Eotaxin may enhance amyloid-beta induced inflammationResearch has demonstrated[@furuya2013]:
Increased CCR3 expression in AD hippocampus
Colocalization with amyloid plaques
Correlation between CCR3 and neurofibrillary tangle burden
Eosinophil-derived products in AD brain tissue
Parkinson's Disease In PD, CCR3 contributes to:
Microglial Activation : CCR3 signaling promotes M1 microglial phenotypeNeuroinflammation : Sustained inflammation in substantia nigraDopaminergic Neuron Loss : Inflammatory mediators contribute to neuron deathMultiple Sclerosis
Demyelination : Eosinophils recruited via CCR3 contribute to demyelinationLesion Formation : CCR3+ cells found in active MS lesionsTherapeutic Target : CCR3 antagonists reduce eosinophil-mediated damage in animal modelsStroke and Ischemia
Post-Ischemic Inflammation : CCR3 contributes to inflammatory responseBlood-Brain Barrier Disruption : Eosinophil recruitment via CCR3Secondary Damage : Inflammatory mediators exacerbate injuryTherapeutic Implications
CCR3 Antagonists Several CCR3 antagonists have been developed and tested:
Clinical Applications
Asthma : CCR3 antagonists reduce eosinophilic inflammationAllergic Rhinitis : Blockade reduces nasal eosinophiliaEosinophilic Esophagitis : Clinical trials ongoingNeurodegeneration : Potential for neuroinflammation modulationChallenges
Species Differences : Rodent and human CCR3 differ significantlyReceptor Complexity : Multiple ligands and signaling pathwaysHomeostatic Role : CCR3 has normal physiological functionsSignal Transduction Pathways
Mermaid diagram (expand to render)
Clinical Significance
Biomarkers
Serum CCL11 : Elevated in AD, correlates with progressionCSF Eotaxin : Potential biomarker for neuroinflammationCCR3 Expression : On circulating eosinophils as disease activity markerDiagnostic Applications
Imaging : PET ligands for CCR3 under developmentGenetic Testing : CCR3 polymorphisms associated with allergic diseaseExpression Analysis : CCR3 on immune cells as inflammatory markerKey Publications
[Damico et al., CCR3 in eosinophil recruitment (2009)](https://pubmed.ncbi.nlm.nih.gov/19357708/)
[Rothenberg et al., Eotaxin and eosinophil recruitment (1999)](https://pubmed.ncbi.nlm.nih.gov/10452754/)
[Berkland et al., CCR3 antagonists in asthma/COPD (2015)](https://pubmed.ncbi.nlm.nih.gov/25740489/)
[Furuya et al., CCR3 in AD brain (2013)](https://pubmed.ncbi.nlm.nih.gov/23726268/)
[Barth et al., Chemokine receptors in CNS (2002)](https://pubmed.ncbi.nlm.nih.gov/12271380/)
[Miller et al., Role of eosinophils in neurodegeneration (2008)](https://pubmed.ncbi.nlm.nih.gov/18692253/)
[Charo & Ransohoff, Chemokine roles in inflammation (2006)](https://pubmed.ncbi.nlm.nih.gov/16481609/)
[Rolls et al., Eosinophils in brain (2007)](https://pubmed.ncbi.nlm.nih.gov/18054267/)
[Wang et al., Targeting CCR3 for treatment (2015)](https://pubmed.ncbi.nlm.nih.gov/25772251/)
[Horuk et al., CCR3 molecular properties (1998)](https://pubmed.ncbi.nlm.nih.gov/9603965/)
[Lucey et al., Eosinophils in MS and EAE (2016)](https://pubmed.ncbi.nlm.nih.gov/27157177/)
[Sullivan et al., CC chemokine receptors in nervous system (2005)](https://pubmed.ncbi.nlm.nih.gov/16054410/)
[Haeger et al., Eosinophils in traumatic brain injury (2006)](https://pubmed.ncbi.nlm.nih.gov/16842756/)
[Kikuchi et al., CCR3 in AD pathology (2019)](https://pubmed.ncbi.nlm.nih.gov/31831028/)
External Resources
[NCBI Gene - CCR3](https://www.ncbi.nlm.nih.gov/gene/1232)
[UniProt - P51671](https://www.uniprot.org/uniprot/P51671)
[Ensembl - CCR3](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00183625)
[OMIM - 601837](https://www.omim.org/entry/601837)
See Also
[CCL11 (Eotaxin-1](/entities/ccl11)
[Eosinophils](/cell-types/eosinophils)
[Neuroinflammation](/mechanisms/neuroinflammation-pathway)
[Alzheimer's Disease](/diseases/alzheimers-disease)
[Parkinson's Disease](/diseases/parkinsons-disease)
[Multiple Sclerosis](/diseases/multiple-sclerosis)
[Chemokine Signaling](/mechanisms/chemokine-signaling-pathway)
[Astrocytes](/entities/astrocytes)
[Microglia](/cell-types/microglia-neuroinflammation)
Pathway Diagram The following diagram shows the key molecular relationships involving CCR3 Gene discovered through SciDEX knowledge graph analysis:
Mermaid diagram (expand to render)
Disease Associations Source: Open Targets Platform (opentargets.org)
| Disease | Association Score | Disease ID |
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