Affinage

CCR2

C-C chemokine receptor type 2 · UniProt P41597

Length
374 aa
Mass
41.9 kDa
Annotated
2026-06-09
100 papers in source corpus 33 papers cited in narrative 34 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CCR2 is a Gi-coupled seven-transmembrane chemokine receptor that drives chemotactic recruitment of classical monocytes and macrophages to inflamed tissues, and its complete loss-of-function in humans abolishes CCL2-dependent monocyte Ca2+ signaling and lung migration, causing pulmonary alveolar proteinosis and polycystic lung disease (PMID:38157855). Cryo-EM of the CCL2–CCR2–G-protein complex shows the chemokine inserting deeply into the extracellular half of the transmembrane domain, with intracellular loop 2 contacts being more critical for G-protein activation than ICL3 (PMID:35570218). Beyond CCL2, CCR2 is activated by additional ligands including CYTL1 (PMID:27084102) and the secreted microprotein PSMP, both driving CCR2-dependent monocyte chemotaxis via Gi/ERK signaling (PMID:31813573, PMID:28698550). CCR2 is also a dual-function receptor that constitutively scavenges extracellular CCL2 by internalizing and recycling independently of G proteins, GRKs, β-arrestins, and clathrin (PMID:36719944), with recycling supported by filamin A trafficking and its phosphorylation at S2152 (PMID:27909248). CCR2 expression is post-transcriptionally controlled through regulated mRNA stability: LPS triggers deadenylation and decay (PMID:9225989, PMID:9365120), while NOX4/HuR signaling stabilizes the transcript (PMID:28383062) and miR-19b-3p suppresses it (PMID:29572892). Functionally, CCR2 governs monocyte egress and tissue infiltration in heart, kidney, lung, liver, and other organs, where CCR2+ macrophages can either amplify inflammation through feed-forward ligand loops (PMID:35404389, PMID:30582448) or support tissue repair and homeostasis (PMID:34749524, PMID:28768911), and CCR2 on cancer cells suppresses anti-tumor immunity by limiting CD103+ DC maturation and upregulating PD-L1 (PMID:32667673).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 1997 High

    Established that CCR2 abundance is set not only by transcription but by regulated mRNA turnover, defining a post-transcriptional control point for receptor expression on activated leukocytes.

    Evidence Nuclear run-on, RNase protection, and mRNA half-life/poly(A) decay measurements in LPS- and IL-2-treated monocytes/NK cells

    PMID:9225989 PMID:9365120

    Open questions at the time
    • Identity of the deadenylase/decay machinery acting on CCR2 mRNA not defined
    • Cis-elements distinguishing CCR2 from ARE-containing chemokine transcripts not mapped
  2. 2008 Medium

    Addressed whether CCR2 has trafficking destinations beyond the plasma membrane by identifying transportin1 as an agonist-enhanced interactor driving receptor nuclear translocation.

    Evidence Bait pulldown, co-immunoprecipitation, nuclear fractionation, and fluorescence imaging

    PMID:18846510

    Open questions at the time
    • Functional consequence of nuclear CCR2 localization not established
    • Interaction shown in a single lab without reciprocal validation
  3. 2016 Medium

    Resolved how activated CCR2 returns to the surface by showing filamin A and its S2152 phosphorylation are required for endosomal recycling.

    Evidence FLNa siRNA knockdown, super-resolution microscopy, phosphosite mutagenesis, and FRAP in CCR2B-expressing cells

    PMID:27909248

    Open questions at the time
    • Kinase responsible for S2152 phosphorylation not identified
    • Single-lab study
  4. 2016 High

    Expanded the CCR2 ligand repertoire beyond CCL2 by demonstrating CYTL1 acts as a functional Gi-coupled agonist driving monocyte chemotaxis.

    Evidence Chemotaxis, internalization, and radioligand binding in HEK293-CCR2B cells plus Ccr2-/- macrophage confirmation and pertussis toxin sensitivity

    PMID:27084102

    Open questions at the time
    • Structural basis of CYTL1–CCR2 engagement not determined
    • Relative physiological contribution versus CCL2 unclear
  5. 2019 High

    Provided atomic-level mechanism of agonist activation, showing CCL2 inserts into the transmembrane core and that ICL2 contacts dominate G-protein activation.

    Evidence Cryo-EM of CCL2–CCR2–G-protein complex with functional mutagenesis

    PMID:35570218

    Open questions at the time
    • Conformational basis of ligand bias or scavenging not captured
    • Structures with alternative ligands (CYTL1, PSMP) not solved
  6. 2019 High

    Identified PSMP as an additional CCR2 ligand driving CCR2-dependent monocyte infiltration and fibrosis, with genetic rescue establishing CCR2 dependence.

    Evidence Psmp-/- mice, AAV8-PSMP overexpression rescue, neutralizing antibody, and in vitro macrophage/LX-2 assays in liver fibrosis models

    PMID:28698550 PMID:31813573

    Open questions at the time
    • Direct PSMP–CCR2 binding affinity not quantified
    • Whether PSMP and CCL2 compete at the same site unknown
  7. 2022 High

    Defined a non-canonical scavenging function: CCR2 constitutively internalizes and recycles CCL2 independently of G proteins, GRKs, β-arrestins, and clathrin, distinguishing it from a signaling-only receptor.

    Evidence CRISPR knockout panels for G proteins, GRKs, β-arrestins, and clathrin with scavenging, internalization, and recycling assays

    PMID:36719944

    Open questions at the time
    • Molecular machinery mediating clathrin-independent internalization unidentified
    • Physiological balance between signaling and scavenging not quantified
  8. 2022 High

    Showed CCR2 on circulating monocytes is required for intravascular monocyte-to-macrophage transition, establishing an autocrine CCR2-ligand feed-forward loop amplifying tissue inflammation.

    Evidence scRNA-seq, CCR2 knockout mice, and monocyte–endothelial cocultures in a glomerulonephritis model

    PMID:35404389

    Open questions at the time
    • Identity of the autocrine CCR2 ligands generated during differentiation not fully resolved
    • Generalizability beyond renal inflammation untested
  9. 2023 High

    Established CCR2 as essential and non-redundant in humans by showing complete loss-of-function abolishes CCL2-dependent monocyte signaling and lung recruitment, causing pulmonary alveolar proteinosis.

    Evidence Human loss-of-function genetics with Ca2+ signaling, migration, and alveolar macrophage enumeration across multiple kindreds

    PMID:38157855

    Open questions at the time
    • Why CCR2 loss specifically manifests as polycystic lung disease mechanistically unclear
    • Therapeutic correction not addressed
  10. 2024 High

    Connected CCR2 macrophage signaling to a transcriptional program by defining a CCR2/ATF3/lysozyme 1/NF-κB axis that drives obesity-induced cardiac inflammation.

    Evidence scRNA-seq, ChIP-PCR, luciferase reporter, and macrophage-specific CCR2 deletion/ablation in obese mouse hearts

    PMID:39056179

    Open questions at the time
    • Direct linkage from CCR2 surface signaling to ATF3 induction not fully reconstituted
    • Relevance to human obese cardiomyopathy untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CCR2 partitions between G-protein signaling and clathrin-independent CCL2 scavenging, and how this balance is tuned across monocyte/macrophage states and tissues, remains unresolved.
  • No structural or molecular model of the scavenging endocytic route
  • Determinants selecting signaling versus scavenging fate of internalized receptor unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 3 GO:0038024 cargo receptor activity 2 GO:0048018 receptor ligand activity 2
Localization
GO:0005768 endosome 2 GO:0005886 plasma membrane 2 GO:0005635 nuclear envelope 1
Pathway
R-HSA-168256 Immune System 5 R-HSA-1500931 Cell-Cell communication 3 R-HSA-162582 Signal Transduction 2
Partners
CCL2CYTL1FLNAPSMPTNPO1

Evidence

Reading pass · 34 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2022 Cryo-EM structure of the CCL2-CCR2-G-protein complex reveals that CCL2 inserts deeply into the extracellular half of the transmembrane domain, with the N-terminal glutamine of CCL2 forming key interactions. Interactions around intracellular loop 2 (ICL2) of CCR2 are conserved and play a more critical role in G-protein activation than those around ICL3. Extensive hydrophobic and polar interactions between CCR2 and Gα-protein contribute to constitutive receptor activity. Cryo-electron microscopy structure determination of CCL2-CCR2-Gprotein complex, complemented by functional mutagenesis experiments Cell discovery High 35570218
2023 CCR2 functions as a dual-function receptor: it promotes monocyte infiltration via G-protein-coupled signaling in response to CCL2, and it also scavenges CCL2 from the extracellular environment by constitutively internalizing and recycling to the cell surface. The scavenging function occurs independently of G proteins, GRKs, β-arrestins, and clathrin, distinguishing it from canonical GPCR internalization and from other professional chemokine scavenger receptors. CRISPR knockout cell lines for G proteins, GRKs, β-arrestins, and clathrin; CCL2 scavenging and internalization assays; recycling assays Science signaling High 36719944
2019 Molecular dynamics simulations and Markov-state modeling show that orthosteric and allosteric antagonists shift CCR2 into distinct stable inactive conformations and disrupt an internal water and sodium ion pathway, preventing transitions to an active-like state. A cryptic drug-binding pocket near the allosteric site was identified in metastable conformations. Long-timescale molecular dynamics simulations coupled with Markov-state model theory; computational structural analysis Proceedings of the National Academy of Sciences of the United States of America Low 30975755
2008 CCR2 directly interacts with transportin1 (TRN1), an interaction that increases upon agonist treatment and promotes CCR2 nuclear translocation in a TRN1-dependent manner. Following translocation, the receptor localizes at the outer edge of the nuclear envelope where it is released from TRN1. Modified CCR2 used as bait to identify interacting proteins; co-immunoprecipitation; nuclear fractionation; fluorescence imaging Proteomics Medium 18846510
2016 Filamin A (FLNa) is required for proper endosomal trafficking and recycling of activated CCR2B. In FLNa-knockdown cells, activated CCR2B accumulates in enlarged EEA-1-positive early endosomes. CCR2B and β2AR signaling induces phosphorylation of FLNa at residue S2152, and this phosphorylation event contributes to sustaining CCR2B recycling back to the plasma membrane. FLNa siRNA knockdown; super-resolution microscopy; endosomal localization assays; phosphorylation site mutagenesis; FRAP Journal of cell science Medium 27909248
2016 CYTL1 (cytokine-like 1) is a functional ligand for CCR2B. CYTL1 induces chemotaxis of human monocytes via CCR2B and the CCR2B-ERK signaling pathway. This was demonstrated by chemotaxis, receptor internalization, and radioactive binding assays in HEK293 cells expressing CCR2B, and confirmed in macrophages from wild-type but not Ccr2-/- mice. CYTL1 activity is sensitive to pertussis toxin, indicating Gi-protein coupling. Chemotaxis assays, receptor internalization assays, radioactive ligand binding assays in HEK293-CCR2B cells; Ccr2-/- macrophage chemotaxis; pertussis toxin inhibition Journal of immunology (Baltimore, Md. : 1950) High 27084102
1997 CCR2 mRNA stability is regulated by LPS through a two-step process: first deadenylation, then degradation of the mRNA body. LPS does not affect the rate of nuclear transcription of CCR2 but reduces mRNA half-life. IL-2 augments CCR2 mRNA levels in monocytes and NK cells. The predominant CCR2 transcript in activated NK cells and mononuclear phagocytes is a long (3.4 kb) form consisting of CCR2B followed by a novel sequence (X) and a CCR2A-specific portion. Northern blotting, RNase protection assays, nuclear run-on transcription assay, mRNA half-life measurements, Poly(A) RNA analysis Journal of leukocyte biology High 9225989 9365120
1997 LPS induces rapid deadenylation followed by degradation of CCR2 mRNA body, demonstrating that post-transcriptional mRNA stability regulation is a mechanism controlling CCR2 expression levels. This is distinct from chemokine mRNAs that contain ARE motifs and are stabilized by LPS. mRNA half-life analysis; Poly(A) CCR2 mRNA decay measurements; comparison with CCR2 nuclear transcription rates by run-on assay Journal of leukocyte biology High 9365120
2001 The anti-CCR2 monoclonal antibody MC-21 blocks ligand binding to murine CCR2 with an IC50 of 0.09 μg/ml, reduces murine MCP-1 (CCL2) activity by 95%, and almost completely prevents monocyte influx in thioglycollate-induced peritonitis. CCR2 is homogeneously expressed on murine monocytes and 2–15% of T cells. mAb generation; ligand-induced CCR2 internalization assay; in vivo peritonitis model with antibody blockade; flow cytometry Journal of immunology (Baltimore, Md. : 1950) Medium 11254730
2019 Tissue-resident CCR2+ cardiac macrophages promote monocyte recruitment through an MYD88-dependent mechanism that results in release of monocyte chemoattractant proteins (MCPs) and monocyte mobilization. In contrast, tissue-resident CCR2- cardiac macrophages inhibit monocyte recruitment. Selective depletion of either population before myocardial infarction has divergent effects on cardiac function and remodeling. Syngeneic cardiac transplantation; intravital 2-photon microscopy; CCR2-DTR and CD169-DTR selective depletion; single-cell RNA sequencing; MYD88-dependent pathway analysis Circulation research High 30582448
2022 CCR2 on circulating monocytes is required for their transition into immature macrophages within the inflamed vasculature. This transition begins intravascularly and relies on CCR2 in circulating cells and TNFR2 in parenchymal cells. Mechanistically, TNF-TNFR2-activated endothelial cells generate CCR2 ligands that drive monocyte differentiation, establishing a CCR2-based autocrine feed-forward loop amplifying renal inflammation. Single-cell RNA sequencing; in vitro monocyte-endothelial cell co-culture; CCR2 knockout mice; flow cytometry; glomerulonephritis mouse model The Journal of experimental medicine High 35404389
2023 Complete autosomal recessive loss-of-function CCR2 deficiency in humans abolishes CCL2-stimulated Ca2+ signaling in and migration of monocytic cells, demonstrating that CCR2 is required for monocyte CCL2-dependent chemotaxis and for monocyte migration to the lungs. CCR2-deficient patients have high blood CCL2 (elevated due to impaired CCL2 consumption/scavenging) and approximately half the normal alveolar macrophage counts, causing pulmonary alveolar proteinosis and polycystic lung disease. Human genetic study with functional validation: Ca2+ signaling assays, monocyte migration assays, alveolar macrophage enumeration, gene expression profiling in loss-of-function CCR2 patients Cell High 38157855
2019 SphK1 (sphingosine kinase 1) in hepatic stellate cells (HSCs) upregulates CCR2 expression by downregulating miR-19b-3p. miR-19b-3p directly suppresses CCR2 expression in HSCs. This SphK1/miR-19b-3p/CCR2 axis in HSCs contributes to their activation and migration during liver fibrosis. SphK1 knockout mice; bone marrow transplantation; miR-19b-3p overexpression/knockdown; CCR2 expression measurement in HSCs; CCl4 and BDL liver fibrosis models Hepatology (Baltimore, Md.) Medium 29572892
2019 PSMP (PC3-secreted microprotein/MSMP) is a CCR2 ligand that promotes liver fibrosis through CCR2. PSMP induced by HMGB-1 and IL-33 from hepatocytes drives CCR2+ monocyte infiltration into liver, macrophage M1 polarization, and hepatic stellate cell activation via CCR2. Overexpression of PSMP in Psmp-/- mouse livers reversed fibrosis attenuation in a CCR2-dependent manner. Psmp-/- mice; CCl4 and BDL fibrosis models; adeno-associated virus-8 PSMP overexpression; PSMP-neutralizing antibody; in vitro macrophage and LX-2 cell assays; CCR2-dependence confirmed genetically Journal of hepatology High 31813573
2017 PSMP chemoattracts Ly6Chi monocytes in a CCR2-dependent manner, confirmed by in situ chemotaxis and adoptive transfer assays. LPS and muramyl dipeptide induced PSMP expression in colonic epithelial cells, and PSMP promoted M1 macrophages to produce CCL2. In situ chemotaxis assay; adoptive transfer of monocytes; anti-PSMP neutralizing antibody; DSS colitis model; in vitro macrophage stimulation Scientific reports Medium 28698550
2015 A CCR2-positive macrophage subpopulation constitutes the majority of fibrin-internalizing cells in the dermis. Fibrin endocytosis is dependent on plasminogen and plasminogen activator but is independent of fibrinogen receptors αMβ2, ICAM-1, the myeloid cell integrin-binding site on fibrin, or the mannose receptor. Elimination of CCR2-expressing cells diminishes cellular fibrin uptake. Intravital microscopy; CCR2+ cell depletion; fibrin internalization assay; knockout mice for fibrinogen receptors; lysosomal targeting assay Blood Medium 26647393
2004 CCR2 is expressed on murine type II alveolar epithelial cells (AECs) and mediates MCP-1-dependent chemotaxis and wound closure in these non-immune cells. AECs from CCR2-/- mice failed to migrate in response to MCP-1 and showed delayed closure of mechanical wounds compared to wild-type AECs. CCR2 mRNA expression in primary AECs; chemotaxis/haptotaxis assays; mechanical wound closure assay in CCR2-/- vs. wild-type AECs; anti-MCP-1 antibody blockade American journal of physiology. Lung cellular and molecular physiology Medium 14656700
2000 CCR2 mediates MCP-1-dependent haptotactic migration of pleural mesothelial cells (PMCs). IL-2 upregulates CCR2 expression and increases haptotactic migration; LPS initially downregulates CCR2 and decreases migration. Blocking CCR2 with neutralizing antibodies decreases haptotactic response of PMCs to MCP-1. Haptotaxis assay; CCR2 neutralizing antibody blockade; flow cytometry; RT-PCR; PMC cultures with IL-2 and LPS treatment American journal of physiology. Lung cellular and molecular physiology Medium 10710532
2006 CCR2 is expressed in human mesangial cells (HMCs) and mediates direct pro-inflammatory effects. MCP-1 binding to CCR2 on HMCs induces a two-fold increase in ICAM-1 expression at 24 h, enhancing monocyte adhesion. CCR2 blockade with RS102895 prevents MCP-1-induced ICAM-1 upregulation. Mechanical stretch reduces CCR2 mRNA and protein expression in HMCs via an MCP-1-independent mechanism and does not induce ICAM-1 via CCR2. CCR2 antagonist (RS102895) blockade; immunofluorescence; cytofluorimetry; monocyte-HMC adhesion assay; RT-PCR; immunoblotting; flow cytometry Kidney international Medium 16518346
2017 PCSK9 reduces LDL-R expression on monocytes, which in turn decreases LDL-C/LDL-R-mediated CCR2 expression on monocytes, impairing MCP-1-directed monocyte migration. LDL-C increases monocyte CCR2 expression. VSMC-derived PCSK9 (induced via TLR-4/SAPK/JNK signaling) inhibits LDL-C-dependent monocyte chemotaxis toward MCP-1. Conditioned media from LPS-stimulated VSMCs applied to monocytes; recombinant PCSK9; LDL-R blocking antibody; CCR2 expression measurement; monocyte migration assay; kinase inhibitor pharmacology Biochemical and biophysical research communications Medium 28232185
2017 NOX4 in hepatic stellate cells (HSCs) stabilizes CCR2 and CCL2 mRNA by promoting Ser221 phosphorylation and cytoplasmic shuttling of the RNA-binding protein HuR. HSC-specific NOX4 knockout mice showed significantly reduced CCR2 and CCL2 expression in alcohol-induced liver injury. HSC-specific NOX4 KO mice; mRNA half-life measurement; HuR phosphorylation and localization assay; alcohol diet model Scientific reports Medium 28383062
2013 Rab GTPases required for cell surface expression and signal transduction (FAK activation) of CCR2 differ from those required for the CXCR4/CCR2 heterodimer, demonstrating that heterodimer formation alters the anterograde trafficking pathway of CCR2. Dominant negative and wild-type Rab GTPase transfection; biotin-streptavidin cell surface expression assay; FAK activation (signal transduction) assay; PC3 prostate cancer cells Cellular physiology and biochemistry Low 23839224
2016 CCR2 expressed on cancer cells (in addition to monocytes) suppresses anti-tumor adaptive immunity. Deletion of Ccr2 specifically in breast cancer cells increased CTL infiltration and activation, increased CD103+ cross-presenting DCs, upregulated MHC class I, and downregulated PD-L1. CCR2 signaling in cancer cells prevents DC maturation toward the CD103+ subtype and reduces cancer cell sensitivity to CTLs. Orthotopic isograft breast cancer mouse model; Ccr2 deletion in cancer cells (genetic); pharmacological CCR2 inhibition; Batf3-/- mice lacking CD103+ DCs; flow cytometry; tumor growth and survival analysis The Journal of experimental medicine High 32667673
2021 CCR2 signaling in mice promotes infiltration of classical monocytes into the lung and expansion of monocyte-derived cells that play a protective role against SARS-CoV-2. CCR2-deficient mice showed higher viral loads, increased viral dissemination, and elevated inflammatory cytokine responses, demonstrating CCR2-dependent monocyte recruitment is mechanistically required for viral control. Mouse-adapted SARS-CoV-2 infection of CCR2-/- mice; intravital antibody labeling; scRNA-seq of lung homogenates; flow cytometry; viral burden measurement mBio Medium 34749524
2016 CCL2 and CCR2 are required for formation of osteoclasts and foreign body giant cells (FBGC). Bone marrow from CCL2-/- and CCR2-/- mice produced significantly fewer and smaller osteoclasts and FBGC. Addition of exogenous CCL2 to CCL2-/- bone marrow cultures rescued osteoclast and FBGC formation, demonstrating CCL2/CCR2 signaling is required for monocyte/macrophage fusion. CCL2-/- and CCR2-/- mouse bone marrow cultures; rescue with exogenous CCL2; quantification of osteoclast/FBGC number, nuclei, and size Journal of cellular biochemistry Medium 26205994
2004 CCR2 signaling is required for complete skeletal muscle regeneration after freeze injury. CCR2-/- mice showed impaired muscle regeneration, prolonged inflammation, fibrosis, fat infiltration, and impaired strength recovery by day 14–28 post-injury. CCR2 co-localizes with activated macrophages (Mac-3+) and activated muscle precursor cells (myogenin+) in injured muscle, while NCAM expression was more elevated in CCR2-/- injured muscle. CCR2-/- mouse freeze-injury model; histology; immunohistochemistry for CCR2, Mac-3, myogenin, MyoD, NCAM; strength testing FASEB journal Medium 15601671
2018 CCR2 inhibition by a novel scFv (58C) that binds the N-terminal domain of CCR2 (KD = 59.8 nM) inhibits monocyte and cancer cell migration and induces M1 macrophage polarization. Multivalent display of 58C-scFv on liposomes further reduces migration by 25–40% and enhances M1 polarization by 200% over monomeric scFv, demonstrating that multivalent CCR2 engagement amplifies downstream signaling effects on macrophage fate. Phage library affinity selection; KD measurement; migration assay; macrophage polarization assay (iNOS/Arg-1, IL-6/Mgl2 ratios); liposomal multivalent display Molecular pharmaceutics Medium 29791797
2017 Gas6 promotes the specific recruitment of inflammatory CCR2hiCX3CR1lo monocytes during venous thrombosis via Gas6-dependent regulation of CCR2 expression on monocytes and CCL2 expression on endothelial cells. Gas6-dependent CCL2 expression and monocyte migration were mediated via JNK (c-Jun N-terminal kinase) signaling. Gas6-/- mice; anti-CCR2 and anti-CCL2 antibody depletion; flow cytometry; in vitro monocyte migration assay; JNK inhibitor; FeCl3 and flow-reduction deep venous thrombosis models Arteriosclerosis, thrombosis, and vascular biology Medium 28450294
2017 CCR2+ macrophages are the predominant source of IGF2 in the neonatal pancreas and support β cell proliferation via IGF1R-mediated signaling. CCR2-specific depletion in neonatal mice leads to a striking reduction in β cell proliferation, dysfunctional islet phenotypes, and glucose intolerance. Adoptive transfer of CCR2+ myeloid cells rescues these defects. CCR2-specific depletion models; adoptive transfer; gene profiling of pancreatic CCR2+ myeloid cells; β cell proliferation assay; glucose tolerance test JCI insight Medium 28768911
2014 siRNA silencing of CCR2 (siCCR2) delivered via nanoparticles reduces Ly6Chigh monocyte numbers in hearts of mice with autoimmune myocarditis by 69% and is active in both monocytes and bone marrow hematopoietic progenitor cells. siCCR2 reduces migration of bone marrow granulocyte-macrophage progenitors into blood and improves ejection fraction. Nanoparticle-encapsulated siRNA delivery; flow cytometry; histology; cellular MRI with macrophage-avid nanoparticles; cardiac MRI volumetry European heart journal Medium 24950695
2022 CCR2+ macrophages in the inflamed kidney promote monocyte-to-macrophage transition intravascularly. CCR2-dependent monocyte differentiation generates CCR2 ligands that form an autocrine feed-forward loop. Single-cell RNA sequencing of in vitro cocultures defines a CCR2-dependent monocyte differentiation path associated with acquisition of immune effector functions. scRNA-seq of monocyte-endothelial cocultures; CCR2 KO mice; glomerulonephritis mouse model; flow cytometry The Journal of experimental medicine High 35404389
1999 The CCR2-64I polymorphism (V64I substitution) does not alter CCR5 mRNA levels, CCR5 cell surface expression, or CCR5 coreceptor function in CD4+ T cells. CCR2-64I is linked to CCR5 promoter polymorphisms (208G, 303A, 627C, 676A) but these do not affect CCR5 transcriptional activity in transfected reporter constructs. Flow cytometry for CCR5 surface expression; RT-PCR for CCR5/CCR2 mRNA; CCR5 coreceptor function assay; transfected CCR5 promoter reporter constructs Journal of virology Medium 9971830
2007 Alveolar macrophages do not express CCR2 (confirmed by microarray, RT-PCR, and flow cytometry) and do not migrate toward CCL2, in contrast to peripheral blood monocytes. This establishes that CCR2 loss accompanies monocyte-to-alveolar macrophage differentiation in vivo. Microarray analysis; RT-PCR; flow cytometry; migration assay; comparison of peripheral blood monocytes and alveolar macrophages from same donors Journal of inflammation (London, England) Medium 17888174
2024 The obesity-induced functional shift of CCR2-expressing macrophages in the heart is mechanistically mediated by the CCR2/ATF3 (activating transcription factor 3)/lysozyme 1/NF-κB signaling axis. Lysozyme 1 acts as a transcriptional activator by binding to the RelA promoter and driving NF-κB signaling, promoting cardiac inflammation in obesity. Inducible ablation of CCR2+CX3CR1+ macrophages or selective deletion of macrophage CCR2 prevents obesity-induced cardiac dysfunction. scRNA-seq; CUTANA ChIP; luciferase assay; macrophage-specific lentivirus transfection; dual recombinase CCR2+ macrophage ablation; macrophage-specific CCR2 deletion; chromatin immunoprecipitation-PCR Circulation research High 39056179

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2019 Tissue Resident CCR2- and CCR2+ Cardiac Macrophages Differentially Orchestrate Monocyte Recruitment and Fate Specification Following Myocardial Injury. Circulation research 602 30582448
2016 Targeting the CCL2-CCR2 signaling axis in cancer metastasis. Oncotarget 419 26885690
2001 Expression and characterization of the chemokine receptors CCR2 and CCR5 in mice. Journal of immunology (Baltimore, Md. : 1950) 369 11254730
2020 CCL2/CCR2 signaling in cancer pathogenesis. Cell communication and signaling : CCS 264 32471499
2013 Role of chemokine CCL2 and its receptor CCR2 in neurodegenerative diseases. Archives of pharmacal research 179 23771498
2009 Recent developments in CCR2 antagonists. Expert opinion on therapeutic patents 148 19441905
2010 Tickets to the brain: role of CCR2 and CX3CR1 in myeloid cell entry in the CNS. Journal of neuroimmunology 147 20554025
2022 Targeting the CCL2-CCR2 axis for atheroprotection. European heart journal 142 35567558
2018 Sphingosine kinase 1 promotes liver fibrosis by preventing miR-19b-3p-mediated inhibition of CCR2. Hepatology (Baltimore, Md.) 141 29572892
2007 Inhibition of MCP-1/CCR2 pathway ameliorates the development of diabetic nephropathy. Biochemical and biophysical research communications 139 17631861
2004 Chemokine receptor CCR2 involvement in skeletal muscle regeneration. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 138 15601671
2015 CCL2-CCR2 Signaling in Disease Pathogenesis. Endocrine, metabolic & immune disorders drug targets 136 25772168
2014 Role of CCR2 in inflammatory conditions of the central nervous system. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 133 24984897
2017 Monocyte subtypes and the CCR2 chemokine receptor in cardiovascular disease. Clinical science (London, England : 1979) 131 28566450
2014 CCR2 deficiency promotes exacerbated chronic erosive neutrophil-dominated chikungunya virus arthritis. Journal of virology 122 24696480
2014 Silencing of CCR2 in myocarditis. European heart journal 122 24950695
2021 Roles of CCL2-CCR2 Axis in the Tumor Microenvironment. International journal of molecular sciences 114 34445235
2007 CCR2 expression correlates with prostate cancer progression. Journal of cellular biochemistry 109 17216598
2011 Monocyte/macrophage chemokine receptor CCR2 mediates diabetic renal injury. American journal of physiology. Renal physiology 108 21880831
2023 M2 Macrophage-Derived sEV Regulate Pro-Inflammatory CCR2+ Macrophage Subpopulations to Favor Post-AMI Cardiac Repair. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 104 36950739
2019 Dual CCR5/CCR2 targeting: opportunities for the cure of complex disorders. Cellular and molecular life sciences : CMLS 104 31377844
2022 Functional Roles of Chemokine Receptor CCR2 and Its Ligands in Liver Disease. Frontiers in immunology 103 35281057
2010 Dual targeting of CCR2 and CCR5: therapeutic potential for immunologic and cardiovascular diseases. Journal of leukocyte biology 92 20360402
2017 CCR2- and CCR2+ corneal macrophages exhibit distinct characteristics and balance inflammatory responses after epithelial abrasion. Mucosal immunology 91 28120849
2016 CCL2/CCR2 signaling pathway in glioblastoma multiforme. Neurochemistry international 91 28025034
2008 Activation of MCP-1/CCR2 axis promotes prostate cancer growth in bone. Clinical & experimental metastasis 91 19002595
2010 CCR2 antagonists. Current topics in medicinal chemistry 79 20536421
2003 Chemokine receptor 2 (CCR2) in atherosclerosis, infectious diseases, and regulation of T-cell polarization. Microcirculation (New York, N.Y. : 1994) 78 12851643
2022 Molecular insights into ligand recognition and activation of chemokine receptors CCR2 and CCR3. Cell discovery 76 35570218
2016 CCL2 and CCR2 are Essential for the Formation of Osteoclasts and Foreign Body Giant Cells. Journal of cellular biochemistry 67 26205994
2019 PSMP/MSMP promotes hepatic fibrosis through CCR2 and represents a novel therapeutic target. Journal of hepatology 64 31813573
2017 CCR2 contributes to the recruitment of monocytes and leads to kidney inflammation and fibrosis development. Inflammopharmacology 63 28168553
2010 Targeting the MCP-1/CCR2 System in diabetic kidney disease. Current vascular pharmacology 63 20180766
2022 Monocytes transition to macrophages within the inflamed vasculature via monocyte CCR2 and endothelial TNFR2. The Journal of experimental medicine 61 35404389
2021 CCR2 deficiency alters activation of microglia subsets in traumatic brain injury. Cell reports 61 34551293
2018 Role of MCP-1 and CCR2 in alcohol neurotoxicity. Pharmacological research 61 30472461
2021 CCR2 Signaling Restricts SARS-CoV-2 Infection. mBio 59 34749524
2020 Loganin alleviates macrophage infiltration and activation by inhibiting the MCP-1/CCR2 axis in diabetic nephropathy. Life sciences 58 33245967
1997 MCP-1 and CCR2 in HIV infection: regulation of agonist and receptor expression. Journal of leukocyte biology 55 9225989
1999 CCR2-64I polymorphism is not associated with altered CCR5 expression or coreceptor function. Journal of virology 52 9971830
2010 Systemic MCP1/CCR2 blockade and leukocyte specific MCP1/CCR2 inhibition affect aortic aneurysm formation differently. Atherosclerosis 51 20197192
2018 CAD1 and CCR2 protein complex formation in monolignol biosynthesis in Populus trichocarpa. The New phytologist 50 30276825
2005 A role for MCP-1/CCR2 in interstitial lung disease in children. Respiratory research 50 16095529
1999 Chemokine receptor CCR2 and CCR5 polymorphisms in children with insulin-dependent diabetes mellitus. Pediatric research 50 10400139
2020 Cancer cell CCR2 orchestrates suppression of the adaptive immune response. The Journal of experimental medicine 49 32667673
2019 MCP1-CCR2 and neuroinflammation in the ALS motor cortex with TDP-43 pathology. Journal of neuroinflammation 49 31666087
2018 Mesenchymal Stem Cells Recruit CCR2+ Monocytes To Suppress Allergic Airway Inflammation. Journal of immunology (Baltimore, Md. : 1950) 47 29352000
1997 Regulation of CCR2 chemokine receptor mRNA stability. Journal of leukocyte biology 47 9365120
2019 Role of CCR2 in the Development of Streptozotocin-Treated Diabetic Cardiomyopathy. Diabetes 46 31439648
2017 PCSK9 regulates the chemokine receptor CCR2 on monocytes. Biochemical and biophysical research communications 46 28232185
2022 Changes in CD163+, CD11b+, and CCR2+ peripheral monocytes relate to Parkinson's disease and cognition. Brain, behavior, and immunity 45 35026420
2023 Human inherited CCR2 deficiency underlies progressive polycystic lung disease. Cell 44 38157855
2018 Modulating Macrophage Polarization through CCR2 Inhibition and Multivalent Engagement. Molecular pharmaceutics 43 29791797
2022 CCR2+ Macrophages Promote Orthodontic Tooth Movement and Alveolar Bone Remodeling. Frontiers in immunology 41 35185928
2019 Salt increases monocyte CCR2 expression and inflammatory responses in humans. JCI insight 41 31672939
2006 The MCP-1/CCR2 system has direct proinflammatory effects in human mesangial cells. Kidney international 41 16518346
2015 A CCR2 macrophage endocytic pathway mediates extravascular fibrin clearance in vivo. Blood 40 26647393
2017 Gas6 Promotes Inflammatory (CCR2hiCX3CR1lo) Monocyte Recruitment in Venous Thrombosis. Arteriosclerosis, thrombosis, and vascular biology 39 28450294
2004 Expression and functional implications of CCR2 expression on murine alveolar epithelial cells. American journal of physiology. Lung cellular and molecular physiology 37 14656700
2020 CCR2-targeted micelles for anti-cancer peptide delivery and immune stimulation. Journal of controlled release : official journal of the Controlled Release Society 36 33011241
2021 Targeting the CCL2-CCR2 axis in depressive disorders. Pharmacological reports : PR 33 34031863
2016 Cytokine-like 1 Chemoattracts Monocytes/Macrophages via CCR2. Journal of immunology (Baltimore, Md. : 1950) 33 27084102
2021 CCR2- and Flt3-Dependent Inflammatory Conventional Type 2 Dendritic Cells Are Necessary for the Induction of Adaptive Immunity by the Human Vaccine Adjuvant System AS01. Frontiers in immunology 32 33519816
2021 CCR2 Signaling Promotes Brain Infiltration of Inflammatory Monocytes and Contributes to Neuropathology during Cryptococcal Meningoencephalitis. mBio 31 34311579
2019 Structural basis for ligand modulation of the CCR2 conformational landscape. Proceedings of the National Academy of Sciences of the United States of America 31 30975755
2016 CCL2-CCR2 signaling promotes hepatic ischemia/reperfusion injury. The Journal of surgical research 31 27229110
2023 The dual-function chemokine receptor CCR2 drives migration and chemokine scavenging through distinct mechanisms. Science signaling 30 36719944
2015 Expression pattern of Ccr2 and Cx3cr1 in inherited retinal degeneration. Journal of neuroinflammation 29 26458944
2020 The CCR2/MCP-1 Chemokine Pathway and Lung Adenocarcinoma. Cancers 28 33322474
2011 CCR2-64I gene polymorphism increase susceptibility to oral cancer. Oral oncology 28 21570337
2000 MCP-1 in pleural injury: CCR2 mediates haptotaxis of pleural mesothelial cells. American journal of physiology. Lung cellular and molecular physiology 28 10710532
2024 CCL2-CCR2 signaling axis in obesity and metabolic diseases. Journal of cellular physiology 27 38284280
2022 CCR2 promotes monocyte recruitment and intestinal inflammation in mice lacking the interleukin-10 receptor. Scientific reports 26 35013585
2022 Activin A and CCR2 regulate macrophage function in testicular fibrosis caused by experimental autoimmune orchitis. Cellular and molecular life sciences : CMLS 26 36434305
2024 NFĸB signaling drives myocardial injury via CCR2+ macrophages in a preclinical model of arrhythmogenic cardiomyopathy. The Journal of clinical investigation 25 38564300
2016 Autocrine MCP-1/CCR2 signaling stimulates proliferation and migration of renal carcinoma cells. Oncology letters 25 27602164
2014 Monocytes infiltrate the pancreas via the MCP-1/CCR2 pathway and differentiate into stellate cells. PloS one 25 24416305
2008 Chemokine receptor CCR2 undergoes transportin1-dependent nuclear translocation. Proteomics 25 18846510
2023 Peripheral CCL2-CCR2 signalling contributes to chronic headache-related sensitization. Brain : a journal of neurology 24 37284790
2022 Role of CCR2-Positive Macrophages in Pathological Ventricular Remodelling. Biomedicines 24 35327464
2013 CCR2 and CCR5 genes polymorphisms in benign prostatic hyperplasia and prostate cancer. Human immunology 24 23632061
2007 Alveolar macrophages lack CCR2 expression and do not migrate to CCL2. Journal of inflammation (London, England) 24 17888174
2003 CCR5 and CCR2 gene polymorphisms in hypertensive patients. British journal of biomedical science 22 12680626
2017 The PSMP-CCR2 interactions trigger monocyte/macrophage-dependent colitis. Scientific reports 21 28698550
2017 A CCR2+ myeloid cell niche required for pancreatic β cell growth. JCI insight 21 28768911
2005 Isolation and structures of novel fungal metabolites as chemokine receptor (CCR2) antagonists. The Journal of antibiotics 21 16466022
2000 Ligands for peroxisome proliferator-activated receptor inhibit monocyte CCR2 expression stimulated by plasma lipoproteins. Trends in cardiovascular medicine 19 11282297
2022 Therapeutic CCR2 Blockade Prevents Inflammation and Alleviates Myxomatous Valve Disease in Marfan Syndrome. JACC. Basic to translational science 18 36687269
2021 CCR2 Deficiency Impairs Ly6Clo and Ly6Chi Monocyte Responses in Orientia tsutsugamushi Infection. Frontiers in immunology 18 34290699
2017 NOX4 Regulates CCR2 and CCL2 mRNA Stability in Alcoholic Liver Disease. Scientific reports 18 28383062
2024 Lysozyme 1 Inflamed CCR2+ Macrophages Promote Obesity-Induced Cardiac Dysfunction. Circulation research 17 39056179
2022 CCR2- and CCR5-mediated macrophage infiltration contributes to glomerular endocapillary hypercellularity in antibody-induced lupus nephritis. Rheumatology (Oxford, England) 17 34747459
2022 CCR2 monocytes repair cerebrovascular damage caused by chronic social defeat stress. Brain, behavior, and immunity 17 35063606
2022 Monocyte chemotactic protein (MCP)-1 (CCL2) and its receptor (CCR2) are elevated in chronic heart failure facilitating lung monocyte infiltration and differentiation which may contribute to lung fibrosis. Cytokine 17 36219898
2016 Phosphorylation of filamin A regulates chemokine receptor CCR2 recycling. Journal of cell science 17 27909248
2015 Intravitreal TSG-6 suppresses laser-induced choroidal neovascularization by inhibiting CCR2+ monocyte recruitment. Scientific reports 17 26149224
2013 Anterograde trafficking of CXCR4 and CCR2 receptors in a prostate cancer cell line. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 17 23839224
2008 Phenotypic and functional differences between wild-type and CCR2-/- dendritic cells: implications for islet transplantation. Transplantation 17 18408585
2022 Myeloid CCR2 Promotes Atherosclerosis after AKI. Journal of the American Society of Nephrology : JASN 15 35537780
2021 CCR2 improves homing and engraftment of adipose-derived stem cells in dystrophic mice. Stem cell research & therapy 15 33413615

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