Affinage

CCR1

C-C chemokine receptor type 1 · UniProt P32246

Length
355 aa
Mass
41.2 kDa
Annotated
2026-04-28
100 papers in source corpus 41 papers cited in narrative 41 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CCR1 is a Gαi-coupled seven-transmembrane chemokine receptor that binds multiple CC chemokines — including CCL3/MIP-1α, CCL5/RANTES, CCL7/MCP-3, CCL15, and CCL23 — to drive leukocyte chemotaxis, osteoclastogenesis, and myeloid cell differentiation in diverse inflammatory, fibrotic, and neoplastic contexts (PMID:9329966, PMID:9115216, PMID:15537451, PMID:35064009). Ligand binding triggers Gαi-dependent signaling including calcium mobilization, cAMP inhibition, and ERK1/2 activation, while CCR1 simultaneously exhibits constitutive activity that recruits β-arrestin-2 for G protein-independent internalization and chemokine scavenging (PMID:24056371, PMID:10734056). Proteolytic N-terminal processing of ligands such as CCL15 and CCL23 by inflammatory proteases can enhance CCR1 potency up to 1000-fold, and cryo-EM structures of the CCR1–Gαi complex revealed that conformational switching of Tyr291 allosterically gates β-arrestin pathway engagement, providing a structural basis for biased agonism (PMID:15905581, PMID:34949837). In vivo, CCR1 on neutrophils, macrophages, and CD34⁺ immature myeloid cells mediates their recruitment to sites of inflammation, fibrosis, and tumor invasion, and CCR1 signaling on hematopoietic stem and progenitor cells drives eosinophil and MDSC differentiation through autocrine/paracrine chemokine loops (PMID:14747380, PMID:17369830, PMID:33640900, PMID:35064009).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1997 High

    Establishing CCR1 as a functional chemokine receptor for MIP-1α and RANTES whose deletion protects against systemic inflammatory injury resolved the question of whether CCR1 has a non-redundant role in leukocyte-driven inflammation in vivo.

    Evidence CCR1 knockout mice with pancreatitis-associated lung injury; radioligand binding and chemotaxis in CCR1-transfected cells

    PMID:9115216 PMID:9329966

    Open questions at the time
    • Downstream signaling pathways not yet defined
    • Relative contribution of individual ligands to disease phenotype unknown
  2. 1998 High

    Demonstrating that the RANTES N-terminus is essential for CCR1 activation and that small-molecule antagonists can block CCR1 signaling established the pharmacological tractability of CCR1 and the structural determinants of ligand recognition.

    Evidence Truncated RANTES variants in calcium mobilization and chemotaxis assays; 4-hydroxypiperidine antagonists in binding, acidification, calcium, and migration assays

    PMID:9565366 PMID:9624164

    Open questions at the time
    • No receptor structure available
    • Mechanism of antagonist binding not resolved at atomic level
  3. 2000 High

    Identification of phosphorylation-dependent desensitization, cross-desensitization by CXCR1/CXCR2, and functional CCR1 expression on platelets and astrocytes broadened the receptor's signaling regulation and cellular context beyond classical leukocyte chemotaxis.

    Evidence Alanine-scanning mutagenesis with GTPase/Ca²⁺ assays in RBL-2H3 cells; immunoprecipitation and aggregation assays on human platelets; TGFβ1-induced CCR1 upregulation in astrocytes

    PMID:10696139 PMID:10734056 PMID:11110672

    Open questions at the time
    • Kinases responsible for CCR1 phosphorylation not identified
    • In vivo relevance of platelet CCR1 not tested
  4. 2001 High

    Pharmacological CCR1 blockade with BX471 reducing renal fibrosis after ureteral obstruction, later validated by CCR1 knockout and adoptive transfer, established that CCR1 on leukocytes is the primary driver of inflammatory cell recruitment leading to organ fibrosis.

    Evidence BX471 antagonist in mouse UUO model; CCR1/CCR5 knockout comparison with adoptive transfer of CCR1-deficient leukocytes

    PMID:11805137 PMID:14747380

    Open questions at the time
    • Whether CCR1 on resident renal cells contributes was not fully excluded
    • Fibrotic signaling downstream of CCR1 on recruited cells not dissected
  5. 2005 High

    Discovery that proteolytic N-terminal truncation of CCL15 and CCL23 enhances CCR1 potency up to 1000-fold, and that NFAT2 transcriptionally activates CCR1 during RANKL-induced osteoclastogenesis, defined two key regulatory layers — extracellular ligand processing and transcriptional control — governing CCR1-mediated responses.

    Evidence In vitro protease cleavage with mass spectrometry and CCR1 signaling/chemotaxis assays; CCR1 promoter-luciferase with CsA inhibition and siRNA in osteoclast precursors

    PMID:15905581 PMID:16355273

    Open questions at the time
    • In vivo relevance of truncated ligand forms not established in genetic models
    • Full promoter regulatory elements for CCR1 not mapped
  6. 2005 High

    Genetic epistasis using CCR1−/−, CCR5−/−, and MIP-1α−/− mice demonstrated that CCR1 (not CCR5) mediates MIP-1α-driven neutrophil migration via sequential TNF-α and LTB4 release, resolving receptor-specific signaling hierarchy in immune inflammation.

    Evidence Multiple knockout strains in peritoneal inflammation model with TNF-α/LTB4 measurement

    PMID:15831559

    Open questions at the time
    • Whether this TNF-α→LTB4 cascade applies in all tissues not tested
    • Direct biochemical link between CCR1 and TNF-α secretion machinery unknown
  7. 2007 High

    Showing that CCR1-expressing CD34⁺ immature myeloid cells are recruited to the tumor invasion front via CCL9 and that CCR1 deletion suppresses tumor invasion established CCR1 as a mediator of pro-tumorigenic myeloid cell recruitment.

    Evidence CCR1 knockout in cis-Apc/Smad4 mutant intestinal tumor mouse model with immunohistochemistry for CD34/MMP markers

    PMID:17369830

    Open questions at the time
    • Human relevance of CCL9/CCR1 axis in tumor invasion not directly tested
    • Whether CCR1 on tumor cells themselves contributes was not dissected
  8. 2010 High

    CCR1 knockout in bone revealed that CCR1 regulates not only osteoclast fusion and motility but also osteoblast RANKL expression, establishing a dual role in osteoclast-osteoblast cross-talk via the RANK-RANKL axis.

    Evidence CCR1 knockout mice with bone densitometry, osteoclastogenesis, and osteoblast co-culture assays

    PMID:20571024

    Open questions at the time
    • Intracellular signaling linking CCR1 to RANKL transcription in osteoblasts unknown
    • Whether CCR1 ligand identity differs in bone microenvironment not resolved
  9. 2013 High

    Demonstrating that CCR1 is constitutively active — with basal Gαi coupling, β-arrestin-2 recruitment, and receptor internalization — and that it simultaneously engages Gαi and β-arrestin-2 in a multiprotein complex revealed a scavenging function independent of classical G protein signaling.

    Evidence cAMP, F-actin, migration, and co-immunoprecipitation assays with pertussis toxin in CCR1-expressing cells

    PMID:24056371

    Open questions at the time
    • Structural basis for constitutive activity not yet determined
    • Physiological relevance of constitutive scavenging in vivo not demonstrated
  10. 2021 High

    Cryo-EM structures of CCR1–Gαi with different CCL15 truncations at 2.6–2.9 Å resolved the structural basis for biased agonism: conformational change of Tyr291 rearranges a polar network that allosterically gates β-arrestin engagement, directly answering how ligand processing generates balanced versus biased signaling.

    Evidence Three cryo-EM structures with mutagenesis and pharmacological characterization

    PMID:34949837

    Open questions at the time
    • No structure of CCR1–β-arrestin complex available
    • How Tyr291 conformational switch mechanistically propagates to intracellular surface not fully modeled
  11. 2022 High

    Establishing that tumor-derived factors induce autocrine CCL3/CCL4–CCR1/CCR5 signaling in HSPCs to drive MDSC differentiation (rather than chemotaxis) revealed a non-migratory, differentiation-instructive function of CCR1 in cancer immune evasion.

    Evidence In vivo nanoparticle-mediated gene silencing, HSPC differentiation assays in CCR1/CCR5-deficient mice and human cord blood cells

    PMID:35064009

    Open questions at the time
    • Relative contribution of CCR1 versus CCR5 in MDSC differentiation not fully deconvolved
    • Downstream transcriptional programs linking CCR1 to myeloid fate specification not identified

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of the CCR1–β-arrestin-2 complex, the in vivo relevance of constitutive scavenging activity, and how CCR1 signaling mechanistically switches between chemotactic and differentiation-instructive outputs in hematopoietic progenitors.
  • No CCR1–β-arrestin complex structure
  • Kinases mediating CCR1 constitutive phosphorylation unknown
  • Transcriptional programs downstream of CCR1 in HSPCs not mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 6 GO:0060090 molecular adaptor activity 1
Localization
GO:0005886 plasma membrane 5
Pathway
R-HSA-168256 Immune System 10 R-HSA-162582 Signal Transduction 6 R-HSA-1266738 Developmental Biology 3
Partners
ARRB2CCL15CCL23CCL3CCL5CXCL4GNAI1LZIP

Evidence

Reading pass · 41 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 CCR1 (beta-chemokine receptor) binds MIP-1alpha and RANTES, and its genetic deletion protects mice from pulmonary inflammation secondary to acute pancreatitis, associated with decreased TNF-alpha levels, indicating CCR1 activation is an early event in systemic inflammatory response syndrome. CCR1 knockout mouse model with pancreatitis-associated lung injury readout and cytokine measurement The Journal of clinical investigation High 9329966
1997 MCP-2 (CCL8) uses CCR1 and CCR2B as functional receptors, as demonstrated by high-affinity 125I-MCP-2 binding to CCR1-transfected HEK293 cells and MCP-2-induced chemotaxis of CCR1-transfected cells. Radioligand binding assay and chemotaxis assay using receptor-transfected cells The Journal of biological chemistry High 9115216
1998 Natural N-terminal truncation of RANTES (producing RANTES(3-68)) abolishes its ability to signal through CCR1 and CCR3 (calcium mobilization) while retaining CCR5 activity, demonstrating that the N-terminal domain of RANTES is essential for CCR1 activation. Calcium mobilization assay in receptor-transfected cells; chemotaxis inhibition assay European journal of immunology High 9565366
1998 Small molecule 4-hydroxypiperidine compounds act as functional CCR1 antagonists, inhibiting MIP-1alpha-induced extracellular acidification and Ca2+ mobilization without intrinsic agonist activity, and blocking MIP-1alpha- and RANTES-induced migration of PBMCs. Competitive radioligand binding (Scatchard analysis), extracellular acidification assay, Ca2+ mobilization assay, PBMC chemotaxis assay The Journal of biological chemistry High 9624164
1999 IFN-gamma treatment of human neutrophils causes rapid upregulation of CCR1 and CCR3 mRNA and induces functional CCR1 expression, enabling neutrophils to bind MCP-3 and migrate toward MIP-1alpha, RANTES, MCP-3, MIP-5/HCC2, and eotaxin — responses not seen in untreated neutrophils. mRNA expression (RT-PCR), radioligand binding assay, chemotaxis assay with receptor-specific blocking antibodies and antagonists Journal of immunology High 9886422
1999 CCR1 deficiency in mice enhances Th1 immune responses during nephrotoxic nephritis and increases renal T cell and macrophage recruitment; MIP-1alpha but not RANTES binds CCR1 and induces chemotaxis in CCR1-overexpressing transfected cells. CCR1 knockout mouse model, nephritis disease readout (proteinuria, BUN, crescent formation), reciprocal binding assay with transfected cells The Journal of clinical investigation High 10587518
2000 CCR1 deletion in mice produces significant prolongation of cardiac allograft survival across multiple MHC-mismatch models, and transfer of CD4+ T cells from long-term tolerant CCR1-/- recipients prolongs allograft survival in naive recipients, demonstrating CCR1 is required for acute and chronic allograft rejection. CCR1 knockout mouse model, heterotopic cardiac transplantation across 4 genetic models, adoptive T cell transfer The Journal of clinical investigation High 10619859
2000 CCR1 is expressed as a functional receptor on human platelets (confirmed by immunoprecipitation, Western blot, and flow cytometry), and CCR1 ligands including MIP-1alpha activate platelets to produce Ca2+ signals, aggregation, and granule content release, partly via ADP release and dependent on cell-surface heparan/chondroitin sulfate. Immunoprecipitation, Western blot, flow cytometry, Ca2+ mobilization assay, platelet aggregation assay, glycosaminoglycan cleavage experiments Blood High 11110672
2000 CCR1 expression on primary mouse astrocytes is specifically upregulated at the transcriptional level by TGFbeta1 in a concentration- and time-dependent manner, resulting in increased CCR1 protein and augmented astrocyte migration toward MIP-1alpha. RT-PCR, mRNA half-life measurement, Western blot, chemotaxis assay Glia Medium 10696139
2000 CCR1 deletion results in absence of airway remodeling (goblet cell hyperplasia and subepithelial fibrosis) in fungal allergic airway disease, associated with higher IFN-gamma and lower IL-4, IL-13, and Th2-inducible chemokines, identifying CCR1 as a major contributor to Th2-driven airway remodeling. CCR1 knockout mouse model, Aspergillus fumigatus sensitization/challenge model, histology, cytokine measurement Journal of immunology High 10903765
2000 CCR1 activation and desensitization are regulated by phosphorylation of specific serine/threonine residues in the cytoplasmic tail (S2 and S3 regions); alanine substitution abolishes receptor phosphorylation and desensitization of G protein coupling but not of Ca2+ mobilization. CXCR1 and CXCR2 cross-phosphorylate and cross-desensitize CCR1, while CCR1 cross-phosphorylates CXCR2 but not CXCR1. Stable transfection of epitope-tagged CCR1 in RBL-2H3 cells, phosphorylation assays, GTPase stimulation assay, Ca2+ mobilization, alanine-scanning mutagenesis, co-expression with CXCR1/CXCR2 The Journal of biological chemistry High 10734056
2001 CCR1 blockade with the small-molecule antagonist BX471 reduces interstitial macrophage and lymphocyte infiltration by 40-60% and substantially reduces renal fibrosis (collagen I, interstitial volume) after unilateral ureter obstruction in mice, even with late-onset treatment. Pharmacological antagonism with BX471 in mouse UUO model, histology, FACS, mRNA analysis The Journal of clinical investigation High 11805137
2002 CCL5/RANTES-induced mast cell migration is mediated by both CCR1 and CCR4, as partial blockade of either receptor alone reduces migration and complete inhibition requires simultaneous blockade of both receptors. Receptor expression by flow cytometry, chemotaxis assay with receptor-specific blocking antibodies Biochemical and biophysical research communications Medium 12270118
2003 Trophoblasts acquire CCR1 expression as they differentiate into invasive extravillous trophoblasts (EVTs) in a process dependent on oxygen tension; CCR1 ligands RANTES and MIP-1alpha produced in decidual tissue promote EVT migration in vitro, establishing a chemokine-CCR1 axis in trophoblast invasion. Immunohistochemistry, villous explant culture, EVT isolation, in vitro migration assay, RT-PCR, O2 tension manipulation Development Medium 14530297
2003 CCR1 is expressed on human hepatoma cell lines but not normal liver, and its CCR1 ligands (CCL3, CCL4, CCL5) inhibit forskolin-induced cAMP elevation, demonstrating functional Gi-coupled CCR1 signaling. CCL3 production by hepatoma cells is induced by IL-1alpha and IL-1beta, suggesting an autocrine/paracrine CCL3-CCR1 loop. RT-PCR, immunohistochemistry, cAMP assay in hepatoma cell lines, ELISA for CCL3 The American journal of pathology Medium 12651617
2004 CCR1 but not CCR5 mediates leukocyte recruitment and subsequent renal fibrosis after unilateral ureteral obstruction; adoptive transfer of CCR1-deficient macrophages and T cells into wild-type mice confirms CCR1 on leukocytes is required for their recruitment to obstructed kidneys. CCR1 and CCR5 knockout mice, UUO model, flow cytometry, adoptive transfer of labeled leukocytes, pharmacological blockade with BX471 Journal of the American Society of Nephrology High 14747380
2004 CCR1 expressed on osteoclast (OC) precursors is upregulated by RANKL, and CCR1 ligands (MIP-1alpha, RANTES, MCP-3) stimulate OC precursor chemotaxis, enhance RANKL-induced OC formation through a RANKL-dependent but RANK-expression-independent pathway, and increase OC motility without altering resorption or survival. RT-PCR, chemotaxis assay, osteoclastogenesis assay with RAW264.7 and primary marrow cells, motility/resorption assays, ELISA Journal of bone and mineral research High 15537451
2004 HCMV infection inhibits immature DC migration by internalizing CCR1 and CCR5 from the cell surface; this effect is mediated by early viral replicative events and by HCMV-induced secretion of CCL3, CCL4, and CCL5, as neutralizing antibodies against these chemokines reduce CCR1 downregulation and restore DC migration by ~60%. Flow cytometry for receptor surface expression, DC migration assay, neutralizing antibody treatment, viral replication inhibitors Journal of leukocyte biology Medium 15522919
2004 LZIP (a transcription factor) binds directly to CCR1 (identified by yeast two-hybrid and confirmed by mammalian two-hybrid and co-immunoprecipitation); residues 21-260 of LZIP are essential for CCR1 interaction. LZIP overexpression selectively enhances Lkn-1/CCL15-induced but not MIP-1alpha-, RANTES-, or HCC-4-induced chemotaxis. Yeast two-hybrid, mammalian two-hybrid, co-immunoprecipitation, chemotaxis assay FASEB journal Medium 15001559
2005 Proinflammatory proteases and physiological fluids (including rheumatoid arthritis synovial fluid) cleave the extended N-terminal domains of CCL6, CCL9, CCL15, and CCL23, activating these 'alternative' CCR1 ligands up to 1000-fold in CCR1-mediated signaling and chemotaxis assays in vitro; the truncated forms are resistant to further cleavage. In vitro protease cleavage assay, CCR1 signaling assay, chemotaxis assay, mass spectrometry of synovial fluid chemokines Journal of immunology High 15905581
2005 MIP-1alpha mediates neutrophil migration in immune inflammation via CCR1 (not CCR5) by inducing sequential release of TNF-alpha and LTB4; CCR1-/- mice fail to respond to OVA or MIP-1alpha with neutrophil migration, while CCR5-/- mice respond normally. CCR1-/- and CCR5-/- mice, MIP-1alpha-/- mice, TNF receptor 1-/- mice, in vivo peritoneal immune inflammation model, LTB4/TNF-alpha measurement Journal of leukocyte biology High 15831559
2005 MIP-1alpha promotes osteoclastogenesis and myeloma cell adhesion to stromal cells via CCR1 (as well as CCR5); blocking CCR1 with neutralizing antibodies or the CCR1-specific antagonist BX471 inhibits OCL formation and upregulation of beta1 integrin mRNA in myeloma cells, and reduces myeloma-stromal cell IL-6 production. RT-PCR, osteoclastogenesis assay, neutralizing antibodies to CCR1 and CCR5, CCR1-specific antagonist BX471, adhesion assay, IL-6 ELISA Experimental hematology High 15730850
2005 CCR1 acts downstream of NFAT2 in RANKL-stimulated osteoclastogenesis; RANKL induces CCR1 promoter activity in a cyclosporin A (CsA)-suppressible manner, and CCR1 siRNA or CCR1 antagonist Met-RANTES inhibit cell migration and multinucleated cell formation. Microarray, quantitative RT-PCR, luciferase reporter assay, siRNA knockdown, Boyden chamber migration assay, CsA inhibition of NFAT Journal of bone and mineral research High 16355273
2005 CCL23 promotes endothelial cell migration and angiogenesis through CCR1; pertussis toxin or anti-CCR1 antibody completely inhibits CCL23-induced endothelial cell migration, and CCL23 does not promote migration of CCR1-negative HT1080 cells. Chemotaxis assay, CAM angiogenesis assay, pertussis toxin treatment, anti-CCR1 antibody blocking, CCR1-negative control cells Cytokine Medium 15927850
2006 The predicted 3D structure of CCR1 identified Tyr-113, Tyr-114 (TM3) and Ile-259 (TM6) as key residues for BX471 antagonist binding; 17 point mutants validated predictions through competitive ligand binding and chemotaxis assays. Computational structure prediction (MembStruk), site-directed mutagenesis of 17 residues, competitive binding assay, chemotaxis assay The Journal of biological chemistry Medium 16837468
2007 CCR1-expressing CD34+ immature myeloid cells (iMCs) migrate toward CCL9 (produced by SMAD4-deficient tumor epithelium), and CCR1 deletion prevents iMC accumulation at the tumor invasion front and suppresses tumor invasion in cis-Apc/Smad4 mutant mice. CCR1 knockout in tumor mouse model, immunohistochemistry for iMC markers (CD34, MMP9, MMP2), CCL9 expression analysis Nature genetics High 17369830
2007 CCR1 deficiency (Ccr1-/-) after myocardial infarction leads to diminished neutrophil infiltration, accelerated monocyte/lymphocyte infiltration, decreased apoptosis, increased proliferation, and earlier myofibroblast population, resulting in smaller infarcts and preserved left ventricular function. CCR1 knockout mouse model, LAD ligation MI model, Langendorff isolated heart preparation, immunohistochemistry, echocardiography Journal of cellular and molecular medicine High 18088392
2008 CCR1 mediates macrophage and neutrophil infiltration into the kidney after renal ischemia-reperfusion injury; CCR1-/- mice have 35% fewer neutrophils and 45% fewer macrophages in injured kidneys, and CCR1-/- injured kidneys have reduced CCL3 and CCL5 levels, suggesting a CCR1-dependent positive feedback loop for leukocyte infiltration. CCR1 knockout mice, pharmacological blockade with BX471, flow cytometry, chemokine ELISA Journal of immunology High 19050287
2010 Overexpression of CCR1 in mesenchymal stem cells (MSCs) dramatically increases chemokine-induced migration and protects MSCs from apoptosis in vitro; CCR1-MSCs accumulate in infarcted myocardium at higher levels, reduce infarct size and cardiomyocyte apoptosis, increase capillary density, and restore cardiac function after MI. CCR1 overexpression in MSCs, in vitro migration and apoptosis assays, intramyocardial injection after coronary artery ligation, histology, echocardiography Circulation research High 20378860
2010 CCR1 deletion in mice causes osteopenia due to impaired osteoclast and osteoblast function; Ccr1-/- osteoclasts show abrogated cell fusion and no osteolytic activity with reduced RANK expression, and Ccr1-/- osteoblasts fail to support osteoclastogenesis due to reduced RANKL expression, establishing CCR1 in osteoclast-osteoblast cross-talk via RANK-RANKL axis. CCR1 knockout mice, bone densitometry, osteoclastogenesis assay, mineralized nodule formation, RT-PCR, co-culture experiments The Journal of biological chemistry High 20571024
2010 CCR1 on human and mouse colon cancer cells (expressing CCL9/CCL15) recruits CCR1+ CD34+ Gr-1- immature myeloid cells that produce MMP2 and MMP9 to promote liver metastasis; genetic deletion of CCR1 or MMP2/MMP9 in the host dramatically suppresses metastatic outgrowth, and CCR1 antagonist BL5923 blocks iMC accumulation and prolongs survival. CCR1 knockout mouse model, liver dissemination model, immunohistochemistry, CCR1 antagonist treatment, survival analysis PNAS High 20616008
2012 Neutrophil Ccr1 amplifies late renal immunopathology in invasive candidiasis by mediating excessive neutrophil recruitment from blood to kidney; Ccr1-/- mice have selectively impaired neutrophil accumulation in the kidney at late timepoints, improved renal function and survival without affecting fungal burden; adoptive transfer of mixed Ccr1+/+ and Ccr1-/- neutrophils confirms cell-autonomous CCR1-dependent trafficking. CCR1 knockout mice, candidiasis model, flow cytometry, adoptive transfer of mixed donor neutrophils, ex vivo chemotaxis assay PLoS pathogens High 22916017
2013 CCR1 exhibits constitutive activity leading to basal cAMP inhibition, increased F-actin, and basal leukocyte migration; constitutive receptor phosphorylation recruits beta-arrestin-2 and drives G protein-independent receptor internalization. CCR1 simultaneously engages Gαi and beta-arrestin-2 in a multiprotein complex, and pertussis toxin-insensitive chemokine uptake suggests a scavenging function via the CCR1·beta-arrestin-2 complex. cAMP assay, F-actin measurement, migration assay, co-immunoprecipitation of CCR1/Gαi/beta-arrestin-2 complex, receptor internalization assay, pertussis toxin treatment The Journal of biological chemistry High 24056371
2013 CCR1/CCL5 interaction in taxane-resistant prostate cancer cells (PC3PR) promotes invasion by activating ERK1/2 and Rac1/cdc42 signaling and increasing secretion of MMP-2 and MMP-9; CCR1 siRNA knockdown reduces all these effects and decreases invasion in Matrigel assay. siRNA knockdown, Western blot for p-ERK1/2 and Rac1/cdc42, MMP-2/9 secretion assay, Matrigel invasion assay, MEK1/2 inhibitor Cytokine Medium 23876400
2013 TNFα and IL-1β induce CCL3 expression in nucleus pulposus cells via NF-κB (p65/IKKβ), MAPK, and C/EBPβ signaling; CCL3-conditioned medium promotes macrophage migration that is blocked by a CCR1 antagonist, establishing the CCL3-CCR1 axis in macrophage infiltration in disc degeneration. Transfection/reporter assay, gain- and loss-of-function for p65/C/EBPβ/p50, lentiviral shRNA (shp65, shIKKβ), Transwell migration assay with CCR1 antagonist Arthritis and rheumatism Medium 23233369
2018 CXCL4/Platelet Factor 4 acts as an agonist of CCR1, inducing CCR1 endocytosis and chemotaxis in CCR1-expressing transfectants and primary human monocytes via a pertussis toxin-sensitive, glycosaminoglycan-dependent mechanism; CCR1 antagonist blocks CXCL4-induced monocyte chemotaxis. Transfected cell migration assay, CCR1 endocytosis assay, pertussis toxin treatment, chondroitinase ABC treatment, CCR1 antagonist blockade, primary human monocyte migration Scientific reports High 29930254
2020 CCR1 activation promotes neuroinflammation after intracerebral hemorrhage via a CCR1/TPR1/ERK1/2 signaling pathway; CCR1 inhibition with Met-RANTES decreases CCR1, TPR1, p-ERK, TNF-α, and IL-1β expression, and these effects are reversed by ERK1/2 activator ceramide C6; TPR1 CRISPR knockdown reverses the neurological effects of rCCL5-induced CCR1 activation. Mouse ICH model, intranasal Met-RANTES, Rac1/ERK1/2 pathway intervention, TPR1 CRISPR, Western blot, immunofluorescence Neurotherapeutics Medium 31898284
2020 Omental macrophages secrete CCL6 (mouse) and CCL23 (human) that promote ovarian cancer migration and colonization via CCR1; CCL6/CCL23 activate ERK1/2 and PI3K signaling in ovarian cancer cells; macrophage depletion and CCR1 inhibition both reduce omental colonization. RNA-sequencing of omental macrophages, macrophage depletion, CCL6/CCL23 knockdown/rescue, CCR1 inhibitor treatment, in vivo omental colonization assay, signaling pathway inhibitors Communications biology High 32963283
2021 Cryo-EM structures of the CCR1-Gi complex (2.6-2.9 Å) bound to different N-terminal truncations of CCL15 reveal that conformational change of Tyr291 (Y291^7.43) triggers polar network rearrangement in the orthosteric binding pocket and allosterically regulates beta-arrestin signaling; different CCL15 truncations act as balanced or biased agonists, identifying a structural basis for natural biased signaling at CCR1. Cryo-EM structure determination (3 structures), pharmacological characterization, computational studies, mutagenesis Nature chemical biology High 34949837
2021 The CCL6-CCR1 axis in hematopoietic stem cells (HSCs) promotes eosinophil differentiation and allergic airway inflammation; CCL6 (produced by eosinophils) acts on CCR1 on HSCs to drive eosinophil differentiation, and CCR1 antagonist BX471 markedly decreases eosinophil differentiation and airway inflammation. Ccl6 knockout mice, OVA challenge model, bone marrow analysis, CCR1 antagonist BX471, flow cytometry Signal transduction and targeted therapy High 33640900
2022 CCR1 and CCR5 on myeloid cells and their precursors mediate cancer-induced MDSC differentiation; tumor-derived factors induce CCL3 and CCL4 in HSPCs that autocrinally engage CCR1 and CCR5 to drive MDSC differentiation (not chemotaxis); silencing CCR1/CCR5 repolarizes PMN-MDSCs into tumoricidal neutrophils and inhibits tumor progression. 4PD nanoparticle-mediated in vivo gene silencing of CCR1/CCR5, flow cytometry, transcriptome analysis, cytokine bead arrays, in vitro HSPC differentiation assay with CCR1/CCR5-deficient mice and human cord blood HSPCs Journal for immunotherapy of cancer High 35064009

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Ccr5 but not Ccr1 deficiency reduces development of diet-induced atherosclerosis in mice. Arteriosclerosis, thrombosis, and vascular biology 240 17138939
2007 SMAD4-deficient intestinal tumors recruit CCR1+ myeloid cells that promote invasion. Nature genetics 233 17369830
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 187 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
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
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 167 23233369
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
1997 Targeted disruption of the beta-chemokine receptor CCR1 protects against pancreatitis-associated lung injury. The Journal of clinical investigation 162 9329966
2010 Inactivation of chemokine (C-C motif) receptor 1 (CCR1) suppresses colon cancer liver metastasis by blocking accumulation of immature myeloid cells in a mouse model. Proceedings of the National Academy of Sciences of the United States of America 151 20616008
2005 Proteolytic activation of alternative CCR1 ligands in inflammation. Journal of immunology (Baltimore, Md. : 1950) 144 15905581
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 123 15569315
2005 MIP-1alpha[CCL3] acting on the CCR1 receptor mediates neutrophil migration in immune inflammation via sequential release of TNF-alpha and LTB4. Journal of leukocyte biology 122 15831559
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
1998 Natural truncation of RANTES abolishes signaling through the CC chemokine receptors CCR1 and CCR3, impairs its chemotactic potency and generates a CC chemokine inhibitor. European journal of immunology 116 9565366
2013 Loss of SMAD4 from colorectal cancer cells promotes CCL15 expression to recruit CCR1+ myeloid cells and facilitate liver metastasis. Gastroenterology 112 23891973
1998 Identification and characterization of small molecule functional antagonists of the CCR1 chemokine receptor. The Journal of biological chemistry 107 9624164
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 98 22916017
2003 Trophoblasts acquire a chemokine receptor, CCR1, as they differentiate towards invasive phenotype. Development (Cambridge, England) 97 14530297
2000 Airway remodeling is absent in CCR1-/- mice during chronic fungal allergic airway disease. Journal of immunology (Baltimore, Md. : 1950) 90 10903765
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
2012 RANTES/CCL5-induced pro-angiogenic effects depend on CCR1, CCR5 and glycosaminoglycans. Angiogenesis 85 22752444
2005 Human CC chemokine CCL23, a ligand for CCR1, induces endothelial cell migration and promotes angiogenesis. Cytokine 84 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
2001 Human CC chemokine liver-expressed chemokine/CCL16 is a functional ligand for CCR1, CCR2 and CCR5, and constitutively expressed by hepatocytes. International immunology 79 11470772
2013 CCR1/CCL5 interaction promotes invasion of taxane-resistant PC3 prostate cancer cells by increasing secretion of MMPs 2/9 and by activating ERK and Rac signaling. Cytokine 77 23876400
2008 Chemokine receptor CCR1 regulates inflammatory cell infiltration after renal ischemia-reperfusion injury. Journal of immunology (Baltimore, Md. : 1950) 77 19050287
2020 Omental macrophages secrete chemokine ligands that promote ovarian cancer colonization of the omentum via CCR1. Communications biology 76 32963283
2011 Spatiotemporal CCR1, CCL3(MIP-1α), CXCR4, CXCL12(SDF-1α) expression patterns in a rat spinal cord injury model of posttraumatic neuropathic pain. Journal of neurosurgery. Spine 76 21332278
2004 Combined blockade of the chemokine receptors CCR1 and CCR5 attenuates chronic rejection. Circulation 74 14757698
2018 CXCL4/Platelet Factor 4 is an agonist of CCR1 and drives human monocyte migration. Scientific reports 72 29930254
2011 Why CCR2 and CCR5 blockade failed and why CCR1 blockade might still be effective in the treatment of rheumatoid arthritis. PloS one 72 21747955
1998 Interferon-gamma increases expression of chemokine receptors CCR1, CCR3, and CCR5, but not CXCR4 in monocytoid U937 cells. Blood 72 9616137
2021 Identification and mechanism of G protein-biased ligands for chemokine receptor CCR1. Nature chemical biology 70 34949837
2006 Pharmacological blockade of CCR1 ameliorates murine arthritis and alters cytokine networks in vivo. British journal of pharmacology 69 17016504
2013 The chemokine receptor CCR1 is constitutively active, which leads to G protein-independent, β-arrestin-mediated internalization. The Journal of biological chemistry 68 24056371
2004 Human cytomegalovirus inhibits the migration of immature dendritic cells by down-regulating cell-surface CCR1 and CCR5. Journal of leukocyte biology 67 15522919
2003 Potential interaction between CCR1 and its ligand, CCL3, induced by endogenously produced interleukin-1 in human hepatomas. The American journal of pathology 67 12651617
1999 CC chemokine receptors, CCR-1 and CCR-3, are potentially involved in antigen-presenting cell function of human peripheral blood monocyte-derived dendritic cells. Blood 66 9864143
2021 Eosinophil-derived chemokine (hCCL15/23, mCCL6) interacts with CCR1 to promote eosinophilic airway inflammation. Signal transduction and targeted therapy 65 33640900
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
2008 Combination of CCR1 mRNA, MCP1, and CA125 measurements in peripheral blood as a diagnostic test for endometriosis. Reproductive sciences (Thousand Oaks, Calif.) 60 19050323
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 59 31898284
2007 Ccr1 deficiency reduces inflammatory remodelling and preserves left ventricular function after myocardial infarction. Journal of cellular and molecular medicine 58 18088392
1987 The effects of ADR1 and CCR1 gene dosage on the regulation of the glucose-repressible alcohol dehydrogenase from Saccharomyces cerevisiae. Molecular & general genetics : MGG 56 3302603
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
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 53 35691078
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
2007 Beneficial effects of CCR1 blockade on the progression of chronic renal allograft damage. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 49 17229070
2017 HIF-2α Promotes Dissemination of Plasma Cells in Multiple Myeloma by Regulating CXCL12/CXCR4 and CCR1. Cancer research 47 28855206
2010 Deficiency of chemokine receptor CCR1 causes osteopenia due to impaired functions of osteoclasts and osteoblasts. The Journal of biological chemistry 47 20571024
1999 Discovery of novel non-peptide CCR1 receptor antagonists. Journal of medicinal chemistry 47 10579830
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
2015 CCR1, an enzyme required for lignin biosynthesis in Arabidopsis, mediates cell proliferation exit for leaf development. The Plant journal : for cell and molecular biology 42 26058952
2000 LEC induces chemotaxis and adhesion by interacting with CCR1 and CCR8. Blood 41 10910894
2012 A knockout mutation in the lignin biosynthesis gene CCR1 explains a major QTL for acid detergent lignin content in Brassica napus seeds. TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik 40 22350089
2007 Downregulation of CCR1 inhibits human hepatocellular carcinoma cell invasion. Biochemical and biophysical research communications 40 17336272
2015 A polymorphism in CCR1/CCR3 is associated with narcolepsy. Brain, behavior, and immunity 39 25986216
2019 MiR-126-3p suppresses the growth, migration and invasion of NSCLC via targeting CCR1. European review for medical and pharmacological sciences 38 30720175
2012 The effect of CCL3 and CCR1 in bone remodeling induced by mechanical loading during orthodontic tooth movement in mice. Bone 38 23059626
2005 BX471: a CCR1 antagonist with anti-inflammatory activity in man. Mini reviews in medicinal chemistry 38 16178722
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
2018 GWAS-identified CCR1 and IL10 loci contribute to M1 macrophage-predominant inflammation in Behçet's disease. Arthritis research & therapy 34 29895319
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
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
2013 Quercetin suppresses MIP-1α-induced adipose inflammation by downregulating its receptors CCR1/CCR5 and inhibiting inflammatory signaling. Journal of medicinal food 31 24325454
2012 Effect of a CCR1 receptor antagonist on systemic trafficking of MSCs and polyethylene particle-associated bone loss. Biomaterials 31 22364730
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
2022 Targeting Chemokine Receptor CCR1 as a Potential Therapeutic Approach for Multiple Myeloma. Frontiers in endocrinology 30 35399952
2017 C-C motif chemokine receptor 1 (CCR1) is a target of the EGF-AKT-mTOR-STAT3 signaling axis in breast cancer cells. Oncotarget 30 29212252
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
2022 CCR1 antagonist ameliorates experimental autoimmune encephalomyelitis by inhibition of Th9/Th22-related markers in the brain and periphery. Molecular immunology 29 35219910
2008 CCR1 antagonists. Molecular diversity 29 18560988
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
2022 CCR1 and CCR5 mediate cancer-induced myelopoiesis and differentiation of myeloid cells in the tumor. Journal for immunotherapy of cancer 27 35064009
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
1997 Characterization of functional chemokine receptors (CCR1 and CCR2) on EoL-3 cells: a model system to examine the role of chemokines in cell function. The Journal of pharmacology and experimental therapeutics 27 9336350
2020 Cigarette smoke-induced lung inflammation in COPD mediated via CCR1/JAK/STAT /NF-κB pathway. Aging 25 32463796
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 25 26501423
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
2007 Treatment with BX471, a nonpeptide CCR1 antagonist, protects mice against acute pancreatitis-associated lung injury by modulating neutrophil recruitment. Pancreas 24 17312463
2005 Chemokine receptor CCR1: a new target for progressive kidney disease. American journal of nephrology 24 16088077
2003 Structure function differences in nonpeptide CCR1 antagonists for human and mouse CCR1. Journal of immunology (Baltimore, Md. : 1950) 24 12574358