Affinage

CCR1

C-C chemokine receptor type 1 · UniProt P32246

Length
355 aa
Mass
41.2 kDa
Annotated
2026-06-09
100 papers in source corpus 43 papers cited in narrative 43 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CCR1 is a CC-chemokine receptor that couples to Gαi to drive leukocyte recruitment and inflammatory tissue remodeling across multiple organs (PMID:14747380, PMID:16355273). It binds a broad set of CC chemokines—including CCL3/MIP-1α, CCL5/RANTES, CCL7/MCP-3, CCL8/MCP-2, CCL14/HCC-1, CCL15, CCL16/LEC, CCL23, and CXCL4—with several promiscuously shared with other receptors (CCR2B, CCR5, CCR8) (PMID:9115216, PMID:9687537, PMID:29930254, PMID:10910894), and many alternative ligands (CCL6, CCL9, CCL15, CCL23) act as weak agonists until proinflammatory proteases remove their N-terminal domains, increasing potency up to 1000-fold (PMID:15905581, PMID:15927850). Ligand engagement signals through pertussis toxin-sensitive Gαi to inhibit adenylyl cyclase and through Gi/Go–PLC–PKCδ–NF-κB to drive chemotaxis (PMID:9687537, PMID:11943214), with a parallel Gα14/16–IL-6–STAT3 autocrine loop producing CXCL8 in macrophages (PMID:23125416); receptor activity is terminated by C-terminal serine/threonine phosphorylation-dependent desensitization that is subject to cross-regulation by CXCR1/CXCR2 (PMID:10734056). Beyond agonist-driven signaling, CCR1 displays constitutive activity, recruiting β-arrestin-2 and undergoing G protein-independent internalization while simultaneously engaging Gαi in a multiprotein complex (PMID:24056371); cryo-EM structures of the CCR1–Gi complex identify Tyr291 (Y291^7.43) in TM7 as the conformational switch governing biased G protein versus β-arrestin signaling, and demonstrate that distinct CCL15 N-terminal truncations act as balanced or biased agonists (PMID:34949837). Functionally, CCR1 mediates cell-intrinsic leukocyte trafficking established by adoptive transfer and bone marrow chimera experiments—including neutrophils, macrophages, and Th1 cells—into kidney, liver, and cardiac allografts (PMID:22916017, PMID:14747380, PMID:19603542, PMID:10619859), and drives osteoclast precursor migration and RANKL-dependent osteoclastogenesis downstream of NFAT2, with CCR1 deficiency causing osteopenia through disrupted osteoblast–osteoclast crosstalk (PMID:16355273, PMID:20571024). CCR1 expression is induced by inflammatory cytokines (IFN-γ, IL-12/STAT4, TGF-β1) on neutrophils, Th1 cells, and astrocytes, broadening the range of CCR1-responsive cell types (PMID:9886422, PMID:10556180, PMID:10696139), and it additionally functions in extravillous trophoblast invasion, platelet and mast cell activation, and post-injury organ fibrosis (PMID:14530297, PMID:11110672, PMID:19592420, PMID:20870892).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1996 Medium

    Established that the CCR1 N-terminal extracellular domain is functionally required for ligand-induced signaling, the first mapping of a receptor region to function.

    Evidence GST-fusion N-terminal polyclonal antibodies blocking calcium mobilization and monocyte chemotaxis in CCR1 transfectants

    PMID:8929558

    Open questions at the time
    • Does not resolve which residues contact ligand
    • Antibody blockade cannot distinguish binding from signaling steps
  2. 1997 High

    Defined CCR1 ligand promiscuity by showing it is a functional receptor for chemokines shared with other CC receptors.

    Evidence Radioligand binding and migration of CCR1- vs CCR2B-transfected HEK293 cells with MCP-2

    PMID:9115216

    Open questions at the time
    • Relative physiological importance of shared vs. exclusive ligands unclear
    • No structural basis for selectivity
  3. 2000 High

    Dissected the molecular basis of CCR1 desensitization and revealed cross-talk between chemokine receptor families.

    Evidence Site-directed mutagenesis of S2/S3 and C-tail, phosphorylation, GTPase, and Ca2+ assays plus cross-desensitization with CXCR1/CXCR2 in RBL-2H3 cells

    PMID:10734056

    Open questions at the time
    • Identity of receptor kinases not established
    • Mechanism of heterologous cross-phosphorylation unresolved
  4. 2002 Medium

    Mapped the downstream signaling cascade for CCR1-driven chemotaxis through defined effectors.

    Evidence Pharmacological inhibition (PTX, PLC, PKCδ, NF-κB) with PLC/PKCδ activity and chemotaxis readouts for CCL15 in HOS cells

    PMID:11943214

    Open questions at the time
    • Inhibitor specificity caveats
    • Newly synthesized proteins required but not identified
  5. 2004 High

    Established cell-autonomous, cell-type-specific roles for CCR1 in leukocyte trafficking and tissue fibrosis in vivo, distinguishing it from CCR5.

    Evidence CCR1-deficient mice with adoptive transfer of labeled macrophages/T cells and BX471 in the UUO renal fibrosis model

    PMID:14747380

    Open questions at the time
    • Specific chemokine ligand(s) driving recruitment in vivo not pinpointed
    • Downstream profibrotic signaling not dissected
  6. 2005 High

    Showed that proteolytic N-terminal truncation is a regulatory switch converting weak CCR1 agonists into potent ones, linking protease activity to chemokine activation in disease.

    Evidence In vitro protease cleavage of CCL6/9/15/23 with signaling/chemotaxis assays and detection of truncated forms in rheumatoid synovial fluid

    PMID:15905581

    Open questions at the time
    • Identity of physiological activating proteases incomplete
    • In vivo contribution of truncation not quantified
  7. 2005 High

    Placed CCR1 in a transcriptional circuit for osteoclastogenesis, establishing NFAT2→CCR1 epistasis.

    Evidence Microarray, NFAT-dependent CCR1 promoter luciferase with cyclosporin A, CCR1 siRNA and Met-RANTES in migration/multinucleation assays

    PMID:16355273

    Open questions at the time
    • Direct NFAT2 binding to CCR1 promoter not shown
    • How migration translates to fusion unresolved
  8. 2010 High

    Genetically established CCR1 as a regulator of bone homeostasis mediating osteoblast–osteoclast crosstalk.

    Evidence CCR1-deficient mice with micro-CT, osteoblast/osteoclast cultures and co-culture rescue of RANK-RANKL signaling

    PMID:20571024

    Open questions at the time
    • Ligand driving the crosstalk in vivo not defined
    • Direct molecular link between CCR1 and RANKL expression unclear
  9. 2012 High

    Demonstrated cell-intrinsic CCR1 requirement for pathogenic neutrophil trafficking using competitive transfer.

    Evidence Competitive adoptive transfer of WT vs Ccr1-/- neutrophils in murine invasive candidiasis

    PMID:22916017

    Open questions at the time
    • Chemokine cues for late-phase recruitment not identified
    • Generalizability to sterile inflammation unclear
  10. 2013 High

    Resolved that CCR1 has functional constitutive activity coupling simultaneously to Gαi and β-arrestin-2, defining two receptor states including a G protein-independent internalizing complex.

    Evidence cAMP, F-actin, migration, phosphorylation, β-arrestin recruitment, co-IP and PTX-insensitive internalization assays

    PMID:24056371

    Open questions at the time
    • Physiological role of constitutive scavenging not established in vivo
    • Stoichiometry of the multiprotein complex unknown
  11. 2021 High

    Provided the structural basis for biased agonism at CCR1, identifying Tyr291 as the conformational switch between G protein and β-arrestin signaling.

    Evidence Cryo-EM structures of CCR1-Gi (ligand-free and CCL15 truncation-bound) with Tyr291 mutagenesis and pharmacology

    PMID:34949837

    Open questions at the time
    • No β-arrestin-bound structure to directly visualize the biased state
    • How endogenous protease-truncated ligands map to balanced/biased outputs in vivo unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CCR1's two signaling modes (Gαi vs constitutive β-arrestin scavenging) are differentially deployed across cell types and disease contexts, and which ligand/truncation states dominate in vivo, remains unresolved.
  • No in vivo evidence linking biased agonism to specific pathologies
  • Physiological chemokine-scavenging function untested
  • Receptor kinases controlling desensitization unidentified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 3
Localization
GO:0005886 plasma membrane 3
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-168256 Immune System 3
Partners
ARRB2CXCR2GNA14GNAI1LZIP/CREB3

Evidence

Reading pass · 43 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2021 Cryo-EM structures of the CCR1-Gi complex (ligand-free and bound to different CCL15 N-terminal truncations) at 2.6–2.9 Å resolution revealed that conformational change of Tyr291 (Y291^7.43) triggers polar network rearrangement in the orthosteric binding pocket and allosterically regulates β-arrestin signaling, establishing the structural basis for biased (G protein vs. β-arrestin) agonism at CCR1. Different N-terminal truncations of CCL15 act as balanced or biased agonists. Cryo-electron microscopy (cryo-EM) structures at 2.6–2.9 Å; pharmacological assays; computational studies; site-directed mutagenesis (Tyr291) Nature Chemical Biology High 34949837
2013 CCR1 exhibits significant constitutive activity in the absence of agonist, leading to basal inhibition of cAMP, increased F-actin, and basal leukocyte migration. Constitutive activity causes basal receptor phosphorylation, recruitment of β-arrestin-2, and subsequent receptor internalization independent of G protein (pertussis toxin-insensitive internalization). CCR1 simultaneously engages Gαi and β-arrestin-2 in a multiprotein complex, suggesting two functional states: canonical Gαi-coupled signaling and a CCR1·β-arrestin-2 complex mediating constitutive G protein-independent internalization with potential chemokine-scavenging function. cAMP assay, F-actin quantification, migration assay, receptor phosphorylation assay, β-arrestin recruitment assay, co-immunoprecipitation, pertussis toxin treatment, receptor internalization assay The Journal of Biological Chemistry High 24056371
2006 Computational prediction of the three-dimensional structure of human CCR1 identified the binding site of the small-molecule antagonist BX 471 (Tyr-113, Tyr-114 on TM3 and Ile-259 on TM6 as key contact residues). Seventeen point mutants validated by competitive ligand binding and chemotaxis experiments confirmed these predictions. Computational structure prediction (MembStruk), site-directed mutagenesis (17 point mutants), competitive ligand binding, chemotaxis assay The Journal of Biological Chemistry Medium 16837468
2009 CCR1 was expressed and purified from an inducible HEK293 system and reconstituted in functional form in n-dodecyl-β-D-maltopyranoside/cholesteryl hemisuccinate detergent, binding CCL14 with a Kd of 21 nM. Function was strictly dependent on detergent composition; phosphocholine detergents yielded non-functional receptor despite maintaining monomeric/small oligomeric state. Recombinant protein expression and purification, fluorescence polarization ligand binding assay, detergent reconstitution Protein Expression and Purification Medium 19275940
2000 CCR1 undergoes ligand-induced phosphorylation and desensitization. Alanine substitution of specific serine/threonine residues (S2 and S3) or C-terminal tail truncation abolished receptor phosphorylation and desensitization of G protein coupling but not desensitization of Ca2+ mobilization. CXCR1 and CXCR2 activation cross-phosphorylates and cross-desensitizes CCR1 at the G protein coupling level. CCR1 cross-desensitizes CXCR2 but not CXCR1. Strength of signaling (greater PI hydrolysis and sustained Ca2+ mobilization) inversely correlates with receptor susceptibility to phosphorylation. Stable transfection in RBL-2H3 cells, phosphorylation assay, GTPase stimulation, Ca2+ mobilization, exocytosis, site-directed mutagenesis (S2, S3, ΔC-tail), cross-desensitization experiments The Journal of Biological Chemistry High 10734056
1997 MCP-2 (CCL8) binds to both CCR1 and CCR2B as functional receptors. Radiolabeled MCP-2 bound to HEK293 cells transfected with CCR1 or CCR2B, and both receptor-transfected cells showed significant migration in response to MCP-2. Radioligand binding (125I-MCP-2), competitive displacement, migration assay with transfected HEK293 cells The Journal of Biological Chemistry High 9115216
1998 HCC-1 (CCL14) specifically activates CCR1 but not closely related receptors (including CCR5). HCC-1 competed with MIP-1α for binding to CCR1-transfected cells with reduced affinity (IC50 = 93 nM vs. 1.3 nM for MIP-1α) and induced adenylyl cyclase inhibition and chemotaxis through CCR1. Cross-desensitization in THP-1 cells, competitive radioligand binding with transfected cells, adenylyl cyclase inhibition assay, chemotaxis assay The Journal of Experimental Medicine High 9687537
2005 Four alternative CCR1 ligands (CCL6/C10, CCL9/MIP-1γ, CCL15/MIP-1δ, CCL23/CKβ8) are weak CCR1 agonists in full-length form but are proteolytically activated up to 1000-fold by proinflammatory proteases that remove their unique N-terminal domains. Truncated CCL15 and CCL23 were detected in synovial fluids of rheumatoid arthritis patients. In vitro protease cleavage, CCR1-mediated signaling assays, chemotaxis assay, detection in synovial fluids Journal of Immunology High 15905581
2018 CXCL4/Platelet Factor 4 drives CCR1-dependent chemotaxis of human monocytes and induces CCR1 endocytosis. CXCL4-induced migration was pertussis toxin-sensitive (implying Gαi coupling), required cell-surface glycosaminoglycans (ablated by chondroitinase ABC), was insensitive to CXCR3 antagonist, and was blocked by a CCR1 antagonist. Chemotaxis assay, CCR1 endocytosis assay, pertussis toxin treatment, chondroitinase ABC treatment, CCR1-expressing transfectants, CCR1 antagonist blockade Scientific Reports Medium 29930254
2002 CCL9/MIP-1γ acts through CCR1 to stimulate cytoplasmic motility and polarization in osteoclasts, identical to effects of CCL3/MIP-1α. CCR1 is the dominant chemokine receptor expressed by osteoclasts; RANKL induces CCL9 to levels comparable to TRAP (a major osteoclast product). Quantitative RT-PCR (SYBR Green real-time), osteoclast migration/motility assay, RANKL stimulation of bone marrow cells Journal of Cellular Biochemistry Medium 12397598
2004 CCR1 promotes osteoclast precursor chemotaxis, RANKL-dependent osteoclastogenesis, and mature osteoclast motility in response to MIP-1α, RANTES, and MCP-3. CCR1 is the most prominent CC receptor in RAW264.7 cells and is upregulated by RANKL. These chemokines directly enhanced osteoclast formation through a RANKL-dependent pathway without altering RANK expression. RT-PCR, CCR1 expression analysis, chemotaxis assay, osteoclast formation assay (marrow and RAW264.7 cells), ELISA for chemokine production Journal of Bone and Mineral Research Medium 15537451
2005 CCR1 acts downstream of NFAT2 in RANKL-stimulated osteoclastogenesis. The CCR1 promoter shows RANKL-dependent and cyclosporin A-suppressible activity (NFAT-dependent). CCR1 siRNA knockdown or CCR1 antagonism (Met-RANTES) abolished osteoclast precursor migration and suppressed multinucleated cell formation. Pertussis toxin also suppressed multinucleation, indicating Gαi-dependent signaling. Microarray analysis, quantitative RT-PCR, luciferase reporter assay, siRNA knockdown, Boyden chamber migration assay, cyclosporin A and pertussis toxin pharmacological inhibition Journal of Bone and Mineral Research High 16355273
2010 CCR1 deficiency in mice causes osteopenia: fewer/thinner trabecular bones and low bone mineral density. CCR1 loss impairs osteoblast differentiation (altered Runx2/Atf4/Osteocalcin expression, disrupted mineralized nodule formation) and reduces osteoclastogenesis via abrogated cell fusion and reduced RANK expression. Co-culture experiments showed CCR1-deficient osteoblasts fail to support osteoclastogenesis, associated with reduced RANKL expression, indicating CCR1 mediates RANK-RANKL crosstalk between osteoclasts and osteoblasts. CCR1-deficient mice, micro-CT/bone histomorphometry, qRT-PCR, in vitro osteoblast and osteoclast cultures, co-culture experiments, mineralized nodule assay The Journal of Biological Chemistry High 20571024
2004 In murine nephrotoxic nephritis, CCR1 deficiency enhanced Th1 immune responses (increased IFNγ, TNF-α, antigen-specific IgG2a, DTH) and worsened glomerulonephritis, rather than simply reducing leukocyte recruitment. MIP-1α (but not RANTES) bound CCR1 and induced cell chemotaxis in reconstitution experiments with CCR1-overexpressing transfected cells. CCR1-deficient mice, nephritis model, antibody titers, cytokine assays, DTH assay, radioligand binding and chemotaxis with CCR1 transfectants The Journal of Clinical Investigation Medium 10587518
2004 CCR1 (but not CCR5) mediates leukocyte recruitment and subsequent renal fibrosis after unilateral ureteral obstruction. Adoptive transfer of labeled CCR1-deficient macrophages/T cells into wild-type UUO mice showed reduced renal recruitment compared to wild-type cells, establishing that CCR1 on leukocytes is required for transendothelial migration into the kidney. CCR1- and CCR5-deficient mice, UUO model, flow cytometry, CCR1 antagonist BX471, adoptive transfer of labeled leukocytes, fibrosis markers Journal of the American Society of Nephrology High 14747380
2009 CCR1 on bone marrow-derived cells (not resident liver cells) mediates profibrogenic effects in hepatic fibrogenesis. CCR1-deficient Kupffer cells show strong suppression of CC chemokine-induced migration. CCR1-deficient mice, chimeric bone marrow transplantation, two fibrosis models (CCl4 and bile duct ligation), macrophage migration assay The Journal of Clinical Investigation High 19603542
2000 CCR1 mediates cardiac allograft rejection. CCR1-deficient mice permanently accepted cardiac allografts across class II MHC mismatch, rejected class I+II mismatched allografts more slowly, and showed no chronic rejection after CD4 antibody treatment. CD4+ T cells from CCR1−/− allograft recipients (tolerized) significantly prolonged allograft survival upon transfer to naïve recipients. CCR1-deficient mice, four cardiac allograft transplant models, cyclosporin A treatment, CD4+ T cell adoptive transfer, histopathology The Journal of Clinical Investigation High 10619859
1999 IFN-γ selectively upregulates CCR1 and CCR3 mRNA and surface expression in human neutrophils, conferring chemotactic responsiveness to MIP-1α, RANTES, MCP-3, MIP-5/HCC2, and eotaxin. Untreated neutrophils do not respond to CC chemokines. CCR2, CCR5, and CXCR1-4 were not upregulated by IFN-γ. RT-PCR, radiolabeled MCP-3 binding assay, chemotaxis assay, antibody blocking (anti-CCR3, aminoxypentane-RANTES) Journal of Immunology Medium 9886422
2000 TGF-β1 selectively upregulates CCR1 mRNA and protein in primary murine astrocytes (but not in hematopoietic cells), resulting in augmented cell migration toward MIP-1α. TGF-β1 increases CCR1 mRNA accumulation at the transcriptional level (mRNA half-life unchanged). Primary astrocyte culture, RT-PCR, Western blot/protein expression, mRNA stability assay (actinomycin D), migration assay Glia Medium 10696139
2004 Human LZIP binds to CCR1 (residues 21–260 of LZIP required) and specifically enhances Lkn-1 (CCL15)-induced chemotaxis through CCR1 without affecting migration induced by other CCR1 ligands (MIP-1α, RANTES, HCC-4). Interaction confirmed by mammalian two-hybrid assay and co-immunoprecipitation. Yeast two-hybrid, mammalian two-hybrid assay, co-immunoprecipitation, deletion mapping, chemotaxis assay FASEB Journal Medium 15001559
2002 CCL15 (Lkn-1)-induced chemotaxis through CCR1 in HOS cells is transduced via Gi/Go protein, phospholipase C, and PKCδ, and requires newly synthesized proteins and NF-κB activation. PLC and PKCδ activities were directly enhanced by Lkn-1 stimulation. Pharmacological inhibitors (pertussis toxin, PLC inhibitor, PKCδ inhibitor, NF-κB inhibitor, cycloheximide, actinomycin D), chemotaxis assay, PLC and PKCδ activity assays, NF-κB DNA binding assay FEBS Letters Medium 11943214
2012 CCR1-mediated STAT3 Tyr705 phosphorylation (nuclear translocation) and CXCL8/IL-8 expression in THP-1 macrophage-like cells involves pertussis toxin-insensitive Gα14/16 signaling and is mediated through an IL-6 autocrine loop. CCL15 activates CCR1→Gα14/16→IL-6→STAT3(Tyr705)→CXCL8. STAT3 Ser727 phosphorylation is distinct, cytosolic, and independent of STAT3 Tyr705. CCR1/Gα14/16 co-expression in HEK293 and THP-1 cells, pertussis toxin treatment, neutralizing anti-IL-6 antibody, STAT3 phosphorylation assays, subcellular fractionation, confocal microscopy, CXCL8 ELISA Journal of Immunology Medium 23125416
2020 CCR1 activation promotes neuroinflammation through a CCR1/TPR1/ERK1/2 signaling pathway after intracerebral hemorrhage in mice. CCR1 agonist (rCCL5) in naïve mice increased TPR1 and p-ERK1/2 expression and neurological deficits; these effects were reversed by TPR1 CRISPR knockdown, placing TPR1 downstream of CCR1 and upstream of ERK1/2. Mouse ICH model, CCR1 antagonist (Met-RANTES), CCR1 agonist (rCCL5), TPR1 CRISPR knockdown, ERK1/2 activator (ceramide C6), Western blot, immunofluorescence, neurobehavioral assays Neurotherapeutics Medium 31898284
2022 CCR1 activation promotes blood-brain barrier disruption via a CCR1/SRC/Rac1 signaling pathway after intracerebral hemorrhage. Pharmacological CCR1 inhibition (Met-RANTES) reduced p-SRC and Rac1 expression and preserved tight junction proteins (claudin-5, occludin, ZO-1); these effects were reversed by Rac1 CRISPR activator. rCCL5-induced BBB disruption in naïve mice was reversed by SRC CRISPR knockout, establishing the CCR1→SRC→Rac1→MMP9/tight junction pathway. Mouse ICH model, Met-RANTES treatment, rCCL5 injection, Rac1 CRISPR activator, SRC CRISPR KO, Western blot, immunofluorescence, brain water content, neurobehavioral assays Fluids and Barriers of the CNS Medium 35062973
2012 CCR1 on neutrophils mediates their late-phase recruitment to the kidney in invasive candidiasis, driving immunopathology and mortality without affecting fungal burden. In competitive adoptive transfer, Ccr1+/+ neutrophils preferentially trafficked to the kidney over Ccr1−/− neutrophils, establishing a cell-intrinsic requirement for CCR1. CCR1-deficient mice, invasive candidiasis model, flow cytometry, ex vivo chemotaxis assay, competitive adoptive transfer of WT vs. CCR1-deficient neutrophils PLoS Pathogens High 22916017
2003 CCR1 is expressed on extravillous trophoblasts (EVTs) as they differentiate to invasive phenotype, but not on cytotrophoblasts or syncytiotrophoblast. CCR1 ligands (RANTES, MIP-1α) produced in decidual tissue promote EVT migration in vitro. CCR1 expression requires relatively high oxygen tension and is reduced by decidua-conditioned medium. Immunohistochemistry, RT-PCR, chorionic villous explant culture, migration assay with isolated EVTs, oxygen tension manipulation Development Medium 14530297
2000 Functional CCR1 is expressed on human platelets. CCR1-activating chemokines (including MIP-1α) induce Ca2+ signals, aggregation, and granule release in platelets. Platelet activation was dependent on ADP release and interaction with ADP receptors, and was inhibited by cleavage of heparan/chondroitin sulfate glycosaminoglycans or by heparin. PCR for mRNA, flow cytometry with specific antibodies, immunoprecipitation, Western blotting, Ca2+ signaling assay, platelet aggregation assay, granule release assay, glycosaminoglycan cleavage Blood Medium 11110672
1996 Polyclonal antibodies against the NH2-terminal portion of CCR1 inhibited calcium mobilization in CCR1 transfectants stimulated with MIP-1α, indicating the N-terminal extracellular domain is critically involved in ligand binding or signaling. The antibody also partially inhibited MIP-1α-induced monocyte chemotaxis. Generation of GST-fusion polyclonal antibodies, calcium mobilization assay in CCR1 transfectants, monocyte chemotaxis inhibition assay, immunofluorescence Journal of Leukocyte Biology Medium 8929558
2001 CCR1 mediates Th1 cell migration. IL-12 (through STAT4 activation) selectively upregulates CCR1 expression on Th1 cells, and CCR1 expression promotes their migration. The pattern of CCR1 upregulation closely mirrors that of integrin α6/β1 and correlates with IL-12/IFN-α signaling kinetics. Th1/Th2 differentiation assay, STAT4 activation analysis, CCR1 expression (RT-PCR, flow cytometry), migration assay Blood Medium 10556180
2002 CCR1 and CCR4 are expressed on human cord blood-derived mast cells. Of seven CCR1 and CCR4 agonists tested, only CCL5/RANTES induces chemotaxis. Migration was partially blocked by anti-CCR1 or anti-CCR4 antibody alone, but completely inhibited when both were blocked simultaneously. RT-PCR, flow cytometry, chemotaxis assay, antibody blocking Biochemical and Biophysical Research Communications Medium 12270118
2004 LEC (CCL16) induces chemotaxis and cell adhesion by binding and activating both CCR1 and CCR8 on transfected HEK-293 cells. LEC induced maximal migration at 89.3 nM and maximal adhesion at 5.6 nM through both receptors. Competitive binding studies, chemotaxis assay, cell adhesion assay with CCR1 and CCR8 transfected HEK-293 cells, neutralizing polyclonal antibody Blood Medium 10910894
2018 The two-site, two-step model for chemokine-CCR1 binding was evaluated and extended to a 'three-step' model. CCR1 N-terminal peptides showed low binding affinities with poor correlation to full-length receptor binding, suggesting other receptor regions contribute to affinity. Using CCL7/CCL2 chimeras, the chemokine N-terminal region contributes significantly to binding affinity but differences in affinity do not completely account for differences in receptor activation, implying a third conformational rearrangement step for activation. Binding affinity measurements with CCR1 N-terminal peptides, CCL7/CCL2 chimera construction, binding and activation assays The Journal of Biological Chemistry Medium 30567735
2009 CCR1 mediates macrophage and neutrophil recruitment to kidney after ischemia-reperfusion injury. CCR1 ligands CCL3 and CCL5 were reduced in injured kidneys from CCR1-deficient mice compared to wild-type, suggesting a CCR1-dependent positive feedback loop for leukocyte infiltration. However, CCR1 deficiency did not affect local leukocyte proliferation, apoptosis, or the extent of tissue necrosis/fibrosis. CCR1-deficient mice, renal ischemia-reperfusion model, CCR1 antagonist BX471, flow cytometry for neutrophils/macrophages, CCL3/CCL5 quantification Journal of Immunology Medium 19050287
2004 CCR1 signaling through its CCL3/CCL6 ligands promotes IL-13-induced lung inflammation and alveolar remodeling. CCR1-null mice had markedly reduced IL-13-induced inflammation, alveolar remodeling, and lower MMP-2, MMP-9, TIMP-4, cathepsins, and MCP-1 expression, comparable to effects of C10/CCL6 neutralization. CCR1-deficient mice, IL-13 transgenic mouse model, C10/CCL6 neutralizing antibody, MMP/TIMP expression analysis, histopathology Journal of Immunology Medium 14734772
2004 CCR1/CCL5 interactions in sepsis exacerbate innate immune responses. CCL5 acted in a CCR1-dependent manner to augment production of IFN-γ and MIP-2 to damaging levels. Peritoneal macrophages from naïve CCR1−/− mice showed enhanced cytokine/chemokine generation and antibacterial responses. CCR1 was not required for leukocyte recruitment in this sepsis model. CCR1-deficient mice, cecal ligation and puncture model, CCL5 administration and neutralization, cytokine profiling, peritoneal macrophage stimulation assays Journal of Immunology Medium 15557190
2010 CCL3/CCR1 signaling mediates thoracic radiation-induced pulmonary fibrosis. Irradiated CCR1-deficient mice (and CCL3-deficient mice) were protected from lung inflammation, fibrosis, and decline in lung function seen in wild-type mice. CCR5-deficient mice were not protected. Small-molecule CCR1 inhibitor also prevented lung inflammation and fibrosis. CCR1-, CCL3-, CCR5-deficient mice, thoracic irradiation model, pharmacological CCR1 inhibitor, hydroxyproline assay, collagen staining, lung function measurement, flow cytometry American Journal of Respiratory Cell and Molecular Biology High 20870892
2010 CCR1 overexpression in mesenchymal stem cells (MSCs) dramatically increased chemokine-induced migration and protected MSCs from apoptosis in vitro. In vivo, CCR1-overexpressing MSCs accumulated preferentially in infarcted myocardium, reduced infarct size, decreased cardiomyocyte apoptosis, and increased capillary density compared to control MSCs. CCR1 overexpression via lentiviral transduction, in vitro migration assay, apoptosis assay, intramyocardial injection of MSCs, histology, cardiac function assessment (Langendorff) Circulation Research Medium 20378860
2021 The CCL6-CCR1 axis in hematopoietic stem cells (HSCs) regulates eosinophil differentiation and allergic airway inflammation. CCL6 (and human orthologs CCL15/CCL23) derived from eosinophils signals through CCR1 on HSCs to promote eosinophil commitment. Ccl6 knockout mice showed reduced allergic airway inflammation, and specific CCR1 antagonist BX471 decreased eosinophil differentiation and airway inflammation. CCL6 knockout mice, OVA challenge model, CCR1 antagonist BX471, flow cytometry, bone marrow analysis Signal Transduction and Targeted Therapy Medium 33640900
2013 TNF-α and IL-1β induce CCL3 expression in nucleus pulposus cells via NF-κB (p65/IKKβ), MAPK, and C/EBPβ pathways. CCL3-conditioned medium from cytokine-treated NP cells promoted macrophage migration, and this was blocked by a CCR1 antagonist, establishing the CCL3-CCR1 axis as the mechanism for macrophage recruitment. qRT-PCR, immunohistochemistry, transfection with promoter constructs, gain/loss of function (NF-κB, C/EBPβ), shRNA for p65 and IKKβ, Transwell migration assay with CCR1 antagonist Arthritis and Rheumatism Medium 23233369
2007 CCR1 deficiency reduces post-myocardial infarction inflammatory remodeling. CCR1-deficient mice showed diminished neutrophil infiltration, accelerated monocyte/lymphocyte infiltration, decreased apoptosis, increased cell proliferation, and earlier myofibroblast population in infarcted tissue, resulting in preserved left ventricular function and reduced infarct expansion. CCR1-deficient mice, coronary artery ligation model, histology, immunohistochemistry, Langendorff isolated heart studies, cardiac function measurements Journal of Cellular and Molecular Medicine Medium 18088392
2005 MIP-1α (CCL3) utilizes both CCR1 and CCR5 to induce osteoclast formation and increase adhesion of myeloma cells to marrow stromal cells. Neutralizing antibodies to CCR1 or CCR5 individually inhibited MIP-1α-induced osteoclast formation and myeloma cell adhesion; CCR1-specific antagonist BX471 also inhibited these effects and beta-1 integrin upregulation in myeloma cells. RT-PCR, neutralizing antibodies to CCR1 and CCR5, CCR1-specific antagonist BX471, osteoclast formation assay, myeloma cell adhesion assay, IL-6 production assay Experimental Hematology Medium 15730850
2005 CCL23 (MPIF-1) promotes angiogenesis through CCR1. CCL23-induced endothelial cell migration and neovascularization were completely inhibited by pertussis toxin or anti-CCR1 antibody, establishing CCR1 as the receptor mediating angiogenic responses. An N-terminal truncated form was at least 100-fold more potent than intact CCL23. Endothelial cell chemotaxis assay, chick chorioallantoic membrane assay, pertussis toxin treatment, anti-CCR1 antibody blockade, control fibrosarcoma cells lacking CCR1 Cytokine Medium 15927850
2009 CCR1 co-stimulation of BMMC (murine bone marrow-derived mast cells) with FcεRI (via IgE cross-linking) enhanced degranulation (85 vs. 54%, p<0.0001) and Ca2+ influx, and significantly increased secretion of TGF-β1, TNF-α, and IL-6 compared to FcεRI stimulation alone. BMMC culture, CCR1 expression by RT-PCR and Western blot, co-stimulation with MIP-1α and antigen/IgE, β-hexosaminidase activity assay, Ca2+ influx assay, cytokine ELISA International Immunology Medium 19592420

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 CCR1 and CCR5 promote hepatic fibrosis in mice. The Journal of clinical investigation 372 19603542
2006 Ccr5 but not Ccr1 deficiency reduces development of diet-induced atherosclerosis in mice. Arteriosclerosis, thrombosis, and vascular biology 241 17138939
2000 Functional expression of CCR1, CCR3, CCR4, and CXCR4 chemokine receptors on human platelets. Blood 201 11110672
2002 A chemokine receptor CCR-1 antagonist reduces renal fibrosis after unilateral ureter ligation. The Journal of clinical investigation 192 11805137
2000 Targeting of the chemokine receptor CCR1 suppresses development of acute and chronic cardiac allograft rejection. The Journal of clinical investigation 188 10619859
2010 Genetic modification of mesenchymal stem cells overexpressing CCR1 increases cell viability, migration, engraftment, and capillary density in the injured myocardium. Circulation research 183 20378860
2013 Tumor necrosis factor α- and interleukin-1β-dependent induction of CCL3 expression by nucleus pulposus cells promotes macrophage migration through CCR1. Arthritis and rheumatism 168 23233369
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
2004 CCR1 chemokines promote the chemotactic recruitment, RANKL development, and motility of osteoclasts and are induced by inflammatory cytokines in osteoblasts. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 166 15537451
2005 Proteolytic activation of alternative CCR1 ligands in inflammation. Journal of immunology (Baltimore, Md. : 1950) 144 15905581
2002 CCL9/MIP-1gamma and its receptor CCR1 are the major chemokine ligand/receptor species expressed by osteoclasts. Journal of cellular biochemistry 126 12397598
1999 Lack of chemokine receptor CCR1 enhances Th1 responses and glomerular injury during nephrotoxic nephritis. The Journal of clinical investigation 126 10587518
2004 CCR1 blockade reduces interstitial inflammation and fibrosis in mice with glomerulosclerosis and nephrotic syndrome. Kidney international 125 15569315
2005 MIP-1alpha utilizes both CCR1 and CCR5 to induce osteoclast formation and increase adhesion of myeloma cells to marrow stromal cells. Experimental hematology 121 15730850
1997 Monocyte chemotactic protein-2 (MCP-2) uses CCR1 and CCR2B as its functional receptors. The Journal of biological chemistry 121 9115216
2007 MLN3897, a novel CCR1 inhibitor, impairs osteoclastogenesis and inhibits the interaction of multiple myeloma cells and osteoclasts. Blood 117 17715391
2001 Increase of CCR1 and CCR5 expression and enhanced functional response to MIP-1 alpha during differentiation of human monocytes to macrophages. Journal of leukocyte biology 112 11272275
2004 Chemokine receptor CCR1 but not CCR5 mediates leukocyte recruitment and subsequent renal fibrosis after unilateral ureteral obstruction. Journal of the American Society of Nephrology : JASN 105 14747380
2012 Chemokine receptor Ccr1 drives neutrophil-mediated kidney immunopathology and mortality in invasive candidiasis. PLoS pathogens 100 22916017
2003 Trophoblasts acquire a chemokine receptor, CCR1, as they differentiate towards invasive phenotype. Development (Cambridge, England) 97 14530297
2006 Role of CCR1 and CCR5 in homing and growth of multiple myeloma and in the development of osteolytic lesions: a study in the 5TMM model. Clinical & experimental metastasis 91 17086356
2004 The C10/CCL6 chemokine and CCR1 play critical roles in the pathogenesis of IL-13-induced inflammation and remodeling. Journal of immunology (Baltimore, Md. : 1950) 87 14734772
2005 Human CC chemokine CCL23, a ligand for CCR1, induces endothelial cell migration and promotes angiogenesis. Cytokine 85 15927850
2006 Essential contribution of a chemokine, CCL3, and its receptor, CCR1, to hepatocellular carcinoma progression. International journal of cancer 83 16284949
2006 Predictions of CCR1 chemokine receptor structure and BX 471 antagonist binding followed by experimental validation. The Journal of biological chemistry 83 16837468
1996 The genes encoding the human CC-chemokine receptors CC-CKR1 to CC-CKR5 (CMKBR1-CMKBR5) are clustered in the p21.3-p24 region of chromosome 3. Genomics 81 8884276
2008 Chemokine receptor CCR1 regulates inflammatory cell infiltration after renal ischemia-reperfusion injury. Journal of immunology (Baltimore, Md. : 1950) 77 19050287
1996 Preparation of specific polyclonal antibodies to a C-C chemokine receptor, CCR1, and determination of CCR1 expression on various types of leukocytes. Journal of leukocyte biology 77 8929558
2021 Identification and mechanism of G protein-biased ligands for chemokine receptor CCR1. Nature chemical biology 76 34949837
2010 Evidences of the cooperative role of the chemokines CCL3, CCL4 and CCL5 and its receptors CCR1+ and CCR5+ in RANKL+ cell migration throughout experimental periodontitis in mice. Bone 76 20053385
2018 CXCL4/Platelet Factor 4 is an agonist of CCR1 and drives human monocyte migration. Scientific reports 74 29930254
2004 Combined blockade of the chemokine receptors CCR1 and CCR5 attenuates chronic rejection. Circulation 74 14757698
2011 Why CCR2 and CCR5 blockade failed and why CCR1 blockade might still be effective in the treatment of rheumatoid arthritis. PloS one 73 21747955
2013 The chemokine receptor CCR1 is constitutively active, which leads to G protein-independent, β-arrestin-mediated internalization. The Journal of biological chemistry 70 24056371
2010 CCR1 antagonists: what have we learned from clinical trials. Current topics in medicinal chemistry 70 20536425
2006 Pharmacological blockade of CCR1 ameliorates murine arthritis and alters cytokine networks in vivo. British journal of pharmacology 69 17016504
2003 Potential interaction between CCR1 and its ligand, CCL3, induced by endogenously produced interleukin-1 in human hepatomas. The American journal of pathology 68 12651617
2000 Distinct expression of CCR1 and CCR5 in glomerular and interstitial lesions of human glomerular diseases. American journal of nephrology 68 10970982
2004 Human cytomegalovirus inhibits the migration of immature dendritic cells by down-regulating cell-surface CCR1 and CCR5. Journal of leukocyte biology 67 15522919
2021 Eosinophil-derived chemokine (hCCL15/23, mCCL6) interacts with CCR1 to promote eosinophilic airway inflammation. Signal transduction and targeted therapy 66 33640900
2007 Temporal expression and cellular origin of CC chemokine receptors CCR1, CCR2 and CCR5 in the central nervous system: insight into mechanisms of MOG-induced EAE. Journal of neuroinflammation 66 17484785
2007 CCR1/CCL5 (RANTES) receptor-ligand interactions modulate allogeneic T-cell responses and graft-versus-host disease following stem-cell transplantation. Blood 65 17641205
2002 Selective CCL5/RANTES-induced mast cell migration through interactions with chemokine receptors CCR1 and CCR4. Biochemical and biophysical research communications 65 12270118
2001 Design, synthesis, and discovery of a novel CCR1 antagonist. Journal of medicinal chemistry 62 11311066
2020 CCR1 Activation Promotes Neuroinflammation Through CCR1/TPR1/ERK1/2 Signaling Pathway After Intracerebral Hemorrhage in Mice. Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics 61 31898284
2004 CCR1 and CC chemokine ligand 5 interactions exacerbate innate immune responses during sepsis. Journal of immunology (Baltimore, Md. : 1950) 61 15557190
2007 Ccr1 deficiency reduces inflammatory remodelling and preserves left ventricular function after myocardial infarction. Journal of cellular and molecular medicine 59 18088392
1999 Upregulation of integrin alpha6/beta1 and chemokine receptor CCR1 by interleukin-12 promotes the migration of human type 1 helper T cells. Blood 59 10556180
2014 CCR1-mediated accumulation of myeloid cells in the liver microenvironment promoting mouse colon cancer metastasis. Clinical & experimental metastasis 57 25326065
2004 Expression of chemokine receptors CCR1 and CCR5 reflects differential activation of mononuclear phagocytes in pattern II and pattern III multiple sclerosis lesions. Journal of neuropathology and experimental neurology 57 15055450
2020 CCL3/CCR1 mediates CD14+CD16- circulating monocyte recruitment in knee osteoarthritis progression. Osteoarthritis and cartilage 56 32006659
2022 The improvement of nonalcoholic steatohepatitis by Poria cocos polysaccharides associated with gut microbiota and NF-κB/CCL3/CCR1 axis. Phytomedicine : international journal of phytotherapy and phytopharmacology 55 35691078
2000 Regulation of the human chemokine receptor CCR1. Cross-regulation by CXCR1 and CXCR2. The Journal of biological chemistry 55 10734056
2010 The chemokine, CCL3, and its receptor, CCR1, mediate thoracic radiation-induced pulmonary fibrosis. American journal of respiratory cell and molecular biology 54 20870892
2006 Progression of kidney disease: blocking leukocyte recruitment with chemokine receptor CCR1 antagonists. Kidney international 52 16374420
2005 Chemokine receptor CCR1 disruption in bone marrow cells enhances atherosclerotic lesion development and inflammation in mice. Molecular medicine (Cambridge, Mass.) 51 16491201
1998 Identification of C-C chemokine receptor 1 (CCR1) as the monocyte hemofiltrate C-C chemokine (HCC)-1 receptor. The Journal of experimental medicine 51 9687537
2010 Deficiency of chemokine receptor CCR1 causes osteopenia due to impaired functions of osteoclasts and osteoblasts. The Journal of biological chemistry 48 20571024
2000 TGFbeta1 selectively up-regulates CCR1 expression in primary murine astrocytes. Glia 45 10696139
2007 Dual role of CCL3/CCR1 in oral squamous cell carcinoma: implications in tumor metastasis and local host defense. Oncology reports 44 17914560
2003 CCR1 chemokine receptor antagonist. Current pharmaceutical design 44 12769747
2012 CCL5, CCR1 and CCR5 in murine glioblastoma: immune cell infiltration and survival rates are not dependent on individual expression of either CCR1 or CCR5. Journal of neuroimmunology 43 22425022
2006 The human specific CCR1 antagonist CP-481,715 inhibits cell infiltration and inflammatory responses in human CCR1 transgenic mice. Journal of immunology (Baltimore, Md. : 1950) 43 16493073
2000 LEC induces chemotaxis and adhesion by interacting with CCR1 and CCR8. Blood 41 10910894
2015 A polymorphism in CCR1/CCR3 is associated with narcolepsy. Brain, behavior, and immunity 40 25986216
2007 Downregulation of CCR1 inhibits human hepatocellular carcinoma cell invasion. Biochemical and biophysical research communications 40 17336272
2019 MiR-126-3p suppresses the growth, migration and invasion of NSCLC via targeting CCR1. European review for medical and pharmacological sciences 38 30720175
2004 Human LZIP binds to CCR1 and differentially affects the chemotactic activities of CCR1-dependent chemokines. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 37 15001559
2003 Differential expression of the chemokine receptors CX3CR1 and CCR1 by microglia and macrophages in myelin-oligodendrocyte-glycoprotein-induced experimental autoimmune encephalomyelitis. Brain pathology (Zurich, Switzerland) 36 14655765
2018 GWAS-identified CCR1 and IL10 loci contribute to M1 macrophage-predominant inflammation in Behçet's disease. Arthritis research & therapy 35 29895319
2011 CCR1 as a target for multiple myeloma. Expert opinion on therapeutic targets 35 21609295
2015 The chemokines CCR1 and CCRL2 have a role in colorectal cancer liver metastasis. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 34 26383527
2013 CCR1 inhibition ameliorates the progression of lupus nephritis in NZB/W mice. Journal of immunology (Baltimore, Md. : 1950) 34 24367031
2003 Developmental changes in the expression of chemokine receptor CCR1 in the rat cerebellum. The Journal of comparative neurology 34 12541321
2005 CCR1 acts downstream of NFAT2 in osteoclastogenesis and enhances cell migration. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 32 16355273
2003 CCR1 is an early and specific marker of Alzheimer's disease. Annals of neurology 32 14595653
2022 Targeting Chemokine Receptor CCR1 as a Potential Therapeutic Approach for Multiple Myeloma. Frontiers in endocrinology 31 35399952
2022 Met-RANTES preserves the blood-brain barrier through inhibiting CCR1/SRC/Rac1 pathway after intracerebral hemorrhage in mice. Fluids and barriers of the CNS 30 35062973
2013 The chemokine CCL5 induces CCR1-mediated hyperalgesia in mice inoculated with NCTC 2472 tumoral cells. Neuroscience 30 24316469
2002 Leukotactin-1/CCL15-induced chemotaxis signaling through CCR1 in HOS cells. FEBS letters 30 11943214
2012 CCR1-mediated STAT3 tyrosine phosphorylation and CXCL8 expression in THP-1 macrophage-like cells involve pertussis toxin-insensitive Gα(14/16) signaling and IL-6 release. Journal of immunology (Baltimore, Md. : 1950) 29 23125416
2008 CCR1 antagonists. Molecular diversity 29 18560988
2022 CCR1 and CCR5 mediate cancer-induced myelopoiesis and differentiation of myeloid cells in the tumor. Journal for immunotherapy of cancer 28 35064009
2021 CCL23 suppresses liver cancer progression through the CCR1/AKT/ESR1 feedback loop. Cancer science 28 34050704
2007 CCR1 and CCR5 chemokine receptors are involved in fever induced by LPS (E. coli) and RANTES in rats. Brain research 28 17604006
2018 Evaluation and extension of the two-site, two-step model for binding and activation of the chemokine receptor CCR1. The Journal of biological chemistry 27 30567735
2009 Expression, purification and in vitro functional reconstitution of the chemokine receptor CCR1. Protein expression and purification 27 19275940
2004 The chemokine receptor CCR1 is strongly up-regulated after skin injury but dispensable for wound healing. Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society 27 15086771
2015 CCL15/CCR1 axis is involved in hepatocellular carcinoma cells migration and invasion. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 26 26501423
2012 CCL5/CCR1 axis regulates multipotency of human adipose tissue derived stromal cells. Stem cell research 26 23276697
2006 Androgen receptor negatively influences the expression of chemokine receptors (CXCR4, CCR1) and ligand-mediated migration in prostate cancer DU-145. Oncology reports 26 16969502
2020 Cigarette smoke-induced lung inflammation in COPD mediated via CCR1/JAK/STAT /NF-κB pathway. Aging 25 32463796
2009 CCR1 expression and signal transduction by murine BMMC results in secretion of TNF-alpha, TGFbeta-1 and IL-6. International immunology 25 19592420
2005 CCR1 antagonists in clinical development. Expert opinion on investigational drugs 25 16022568
2005 Chemokine receptor CCR1: a new target for progressive kidney disease. American journal of nephrology 25 16088077
2023 Blockade of CCR1 induces a phenotypic shift in macrophages and triggers a favorable antilymphoma activity. Blood advances 24 36630565
2016 CCR1 antagonism attenuates T cell trafficking to omentum and liver in obesity-associated cancer. Immunology and cell biology 24 27046081
2005 Plasmodium yoelii 17XL infection up-regulates RANTES, CCR1, CCR3 and CCR5 expression, and induces ultrastructural changes in the cerebellum. Malaria journal 24 16359553
2003 Structure function differences in nonpeptide CCR1 antagonists for human and mouse CCR1. Journal of immunology (Baltimore, Md. : 1950) 24 12574358
2002 Expression of RANTES and CCR1 in oral lichen planus and association with mast cell migration. Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 24 11903822

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