| 1996 |
CMKLR1 (chemokine-like receptor 1) was cloned as a novel human gene encoding a seven-transmembrane G protein-linked receptor with 55% nucleotide homology to the IL-8 type 1 receptor and 53% to the N-formyl peptide related receptor 1, and was localized to human chromosome 12q24.1 by fluorescence in situ hybridization. mRNA is expressed in hematopoietic and immune tissues. |
Molecular cloning, FISH chromosomal mapping, Northern blot/expression analysis |
Cytogenetics and cell genetics |
High |
8976386
|
| 1998 |
CMKLR1 (ChemR23) is expressed abundantly in monocyte-derived dendritic cells and macrophages and functions as a coreceptor for SIV strains (SIVmac316, SIVmac239, SIVmac17E-Fr, SIVsm62A) and a primary HIV-1 strain (92UG024-2) in cell fusion assays, but not for tested HIV-2 strains. |
RT-PCR expression analysis, cell fusion coreceptor assay |
European journal of immunology |
High |
9603476
|
| 2003 |
TIG2 (chemerin, encoded by RARRES2) was identified as the natural ligand of CMKLR1 (ChemR23) through reverse pharmacology screening of a peptide library from human hemofiltrate; the active circulating form corresponds to amino acid residues 21–154 of the 163 aa prepropeptide. |
Reverse pharmacology peptide library screening, biochemical characterization |
FEBS letters |
High |
14675762
|
| 2005 |
CMKLR1 (ChemR23) is expressed and functional on blood plasmacytoid and myeloid dendritic cells; recombinant chemerin induces transmigration of these cells across an endothelial cell monolayer. ChemR23 is expressed on the luminal side of high endothelial venules in secondary lymphoid organs, directing DC trafficking. |
Flow cytometry, transendothelial migration assay, immunohistochemistry |
The Journal of experimental medicine |
High |
15728234
|
| 2007 |
RvE1 binds directly to CMKLR1 (ChemR23) on human PBMC and induces calcium mobilization; it also acts as a partial agonist at BLT1. At higher doses, RvE1's anti-inflammatory actions in vivo are BLT1-independent, consistent with ChemR23-mediated effects. |
[3H]RvE1 radioligand binding assay (membrane fractions), calcium mobilization assay, in vivo peritonitis model with BLT1 KO mice |
Journal of immunology |
High |
17339491
|
| 2008 |
Proteolytically processed murine chemerin and derived C-terminal peptide chemerin15 (C15, residues A140–A154) exert anti-inflammatory effects entirely dependent on ChemR23; C15 suppressed neutrophil and monocyte recruitment in zymosan-induced peritonitis in wild-type but not ChemR23-/- mice, demonstrating absolute ChemR23 dependence. |
In vitro macrophage activation assay, in vivo peritonitis model using ChemR23 knockout mice, neutralizing antibody experiments |
The Journal of experimental medicine |
High |
18391062
|
| 2009 |
Mouse CMKLR1 (ChemR23) is highly expressed on immature plasmacytoid DCs and at lower levels on myeloid DCs, macrophages, and NK cells. Chemerin promotes calcium mobilization and chemotaxis on these cells, and these responses are abrogated in ChemR23 knockout mice. Mouse prochemerin requires C-terminal processing to generate an active ChemR23 agonist. |
Flow cytometry, calcium mobilization assay, chemotaxis assay, ChemR23 KO mice, structural/pharmacological analysis |
Journal of immunology |
High |
19841182
|
| 2009 |
CMKLR1 (ChemR23) is expressed in human endothelial cells and is upregulated by pro-inflammatory cytokines TNF-α, IL-1β, and IL-6. Chemerin acting via ChemR23 induces endothelial angiogenesis, MMP-2 and MMP-9 gelatinolytic activity, and dose-dependently activates PI3K/Akt and MAPK signaling pathways. |
In vitro angiogenesis assays, gelatin zymography, Western blot for PI3K/Akt and MAPK phosphorylation |
Biochemical and biophysical research communications |
Medium |
20044979
|
| 2010 |
Knockdown of CMKLR1 by RNA interference abrogated adipocyte differentiation, clonal expansion, and basal proliferation of bone marrow stromal cells (BMSCs), and was associated with increased osteoblast marker gene expression and mineralization. Forced PPARγ expression induced chemerin and partially rescued loss of adipogenesis caused by CMKLR1 knockdown, placing CMKLR1 downstream of PPARγ in a chemerin autocrine loop. |
siRNA knockdown, adipogenesis/osteoblastogenesis differentiation assays, PPARγ overexpression rescue, primary BMSC cultures |
Journal of bone and mineral research |
High |
19929432
|
| 2010 |
CMKLR1 (ChemR23) promotes phagocytosis of microbial particles and efferocytosis of apoptotic cells in macrophages by a mechanism involving increased actin polymerization and F-actin localization to the phagocytic cup in a Syk kinase-dependent manner; these prophagocytic effects are absent in ChemR23-/- macrophages and completely abrogated by pharmacological Syk inhibition. |
Phagocytosis/efferocytosis assays, ChemR23 KO macrophages, pharmacological Syk inhibition, F-actin imaging, in vivo peritoneal clearance assay |
Journal of immunology |
High |
20363975
|
| 2010 |
Chemerin stimulation of human articular chondrocytes via ChemR23 activates ERK1/2 (p44/p42 MAPK) and Akt (Ser473) phosphorylation and significantly increases secretion of pro-inflammatory cytokines (IL-6, IL-8, TNF-α, IL-1β) and matrix metalloproteases (MMP-1, MMP-2, MMP-3, MMP-8, MMP-13). |
Western blot for phospho-MAPK and phospho-Akt, cytokine ELISA, MMP measurement in cell supernatants, primary chondrocyte cultures |
Arthritis research & therapy |
Medium |
21192818
|
| 2011 |
ChemR23 deficiency in mice leads to reduced plasmacytoid DC recruitment to lungs during viral pneumonia, decreased type I interferon production, and increased neutrophilic infiltration, demonstrating a dual role: ChemR23-dependent pDC recruitment contributes to viral clearance but also promotes inflammation, while a separate ChemR23-dependent anti-inflammatory pathway in non-leukocytic cells reduces morbidity/mortality. |
ChemR23 KO mice, PVM infection model, pDC depletion, adoptive transfer, chimeric mice |
PLoS pathogens |
High |
22072972
|
| 2011 |
CMKLR1 (ChemR23) deficiency in mice results in reduced adiposity (lower body mass and percent body fat), decreased hepatic dendritic cell infiltration, decreased adipose CD3+ T cells, increased adipose NK cells, and impaired glucose-stimulated insulin secretion and glucose uptake in skeletal muscle and white adipose tissue, establishing CMKLR1 as a regulator of adipose development, inflammation, and glucose homeostasis in vivo. |
CMKLR1 KO mouse model, body composition analysis, glucose tolerance/insulin secretion tests, flow cytometry of immune infiltrates, tissue glucose uptake assay |
Endocrinology |
High |
22186410
|
| 2013 |
ChemR23 forms homomers and heteromers with chemokine receptors CCR7 and CXCR4 as demonstrated by BRET and HTRF assays. Negative binding cooperativity was detected between ChemR23 and these chemokine receptors: ligands of one receptor competed for binding of a tracer to the other. In primary mouse bone marrow-derived DCs from wild-type vs ChemR23 KO mice, ChemR23-specific ligands cross-inhibited CXCL12 binding on CXCR4 in a ChemR23-dependent manner. |
BRET assay, HTRF assay, radioligand binding competition, ChemR23 KO bone marrow-derived DCs |
PloS one |
High |
23469143
|
| 2013 |
ChemR23 is expressed in neutrophil granules and is rapidly upregulated upon neutrophil activation. The C15/ChemR23 pathway inhibits integrin activation and clustering, reduces neutrophil adhesion and chemotaxis in vitro, and induces adherent cell detachment from inflamed endothelium in vivo, reducing neutrophil recruitment and heart damage in a murine myocardial infarction model through ChemR23. |
Flow cytometry, immunofluorescence (granule localization), integrin activation assays, intravital microscopy, murine MI model, ChemR23-dependent pharmacological experiments |
EMBO reports |
High |
23999103
|
| 2014 |
CMKLR1 small molecule antagonist α-NETA inhibits chemerin-stimulated β-arrestin2 association with CMKLR1 and chemerin-triggered CMKLR1+ cell migration, and significantly delayed EAE onset and reduced CNS mononuclear cell infiltrates when administered to mice, pharmacologically recapitulating the CMKLR1 KO phenotype. |
β-arrestin2 recruitment assay, cell migration assay, EAE model (active immunization and adoptive transfer), CNS histology |
PloS one |
Medium |
25437209
|
| 2015 |
Chemerin binds to CMKLR1 (and GPR1 and CCRL2) with low nanomolar affinity. Binding of chemerin and the chemerin-9 nonapeptide (149YFPGQFAFS157) to CMKLR1 activates Gαi1, Gαi2, Gαi3, Gαoa, and Gαob (but not Gαs or Gαq), and recruits β-arrestin1 and β-arrestin2. ERK1/2 phosphorylation requires both Gαi/o and β-arrestin2 but not β-arrestin1. GPR1 does not activate G proteins but does recruit β-arrestins. CCRL2 does not activate G proteins or recruit β-arrestins. |
BRET-based biosensors for G protein activation and β-arrestin recruitment, radioligand binding, ERK phosphorylation with pathway-specific inhibitors |
PloS one |
High |
27716822
|
| 2015 |
CMKLR1 is a functional receptor for amyloid-β peptide (Aβ42): Aβ42 binds specifically to CMKLR1 in stably transfected RBL cells, induces CMKLR1-dependent cell migration via ERK1/2, PKA, and Akt pathways (but not Ca2+ mobilization), and stimulates internalization of the Aβ42-CMKLR1 complex in microglia and CMKLR1-RBL cells. |
Radioligand-equivalent binding in stably transfected RBL cells, migration assays (N9 microglia, primary microglia, CMKLR1-RBL vs untransfected RBL), pathway inhibitor studies, internalization assay |
Journal of Alzheimer's disease |
Medium |
25079809
|
| 2015 |
CMKLR1 signals through a RhoA/ROCK-dependent pathway to activate the transcriptional regulator SRF; chemerin-mediated chemotaxis requires p38, Gαi/o, RhoA, and ROCK signaling. Species-specific and receptor-dependent differences in GPR1 and CMKLR1 signaling were demonstrated. |
Luciferase reporter assays (SRF, CRE, NF-κB), pathway-specific inhibitors, chemotaxis assay in L1.2 and AGS cells |
Molecular and cellular endocrinology |
Medium |
26363224
|
| 2015 |
ChemR23 is differentially expressed in macrophage polarization states: LPS or IFN-γ stimulation increases transcription from promoter P3 in M1 macrophages. M1 macrophages expressing ChemR23 are chemotactic to chemerin, while M2 macrophages without surface ChemR23 are not. RvE1 (10 nM) acting through ChemR23 on M1 macrophages increases IL-10 transcription and phagocytosis of microbial particles, driving resolution-type repolarization. |
5' RACE (promoter identification), flow cytometry, qPCR, chemotaxis assay, phagocytosis assay, primary human macrophages |
Journal of immunology |
High |
25637017
|
| 2016 |
Chemerin exerts vasoconstrictor actions via CMKLR1 but not GPR1 in human and rat vasculature: the chemerin C-terminal peptide C9 (chemerin149-157) contracted human saphenous vein and resistance arteries and increased blood pressure in rats, and these effects were blocked by the selective CMKLR1 antagonist CCX832. C9 inhibited cAMP accumulation in human aortic smooth muscle cells and showed ~5000-fold bias toward Gi protein signaling over other pathways (biased agonism at CMKLR1). |
Isometric tension (vascular contraction), blood pressure measurement in rats, cAMP accumulation assay, selective antagonist CCX832, immunohistochemistry for receptor localization |
Journal of the American Heart Association |
High |
27742615
|
| 2016 |
Nanobodies (CA4910 and CA5183) targeting the native conformation of ChemR23 bind to a site overlapping with the chemerin binding site and act as antagonists of chemerin-induced intracellular calcium increase and chemotaxis of human primary cells. A bivalent CA4910 nanobody showed enhanced antagonist efficacy. The chemerin C-terminal nonapeptide (chemerin149-157) binding site on ChemR23 largely overlaps with the chemerin binding site. |
Phage display/genetic immunization (nanobody development), competition binding assays, calcium mobilization assay, chemotaxis assay, flow cytometry with primary cells |
Journal of immunology |
High |
26864035
|
| 2018 |
Targeted deletion of the resolvin E1 receptor Erv1/ChemR23 in hyperlipidemic mice (Apoe-/-) leads to proatherogenic macrophage signaling, increased oxidized LDL uptake, reduced phagocytosis, and increased atherosclerotic plaque size and necrotic core formation. RvE1-mediated effects on oxLDL uptake and phagocytosis in macrophages are dependent on Erv1/ChemR23. |
ChemR23/Apoe double KO mice, histological plaque analysis, macrophage phagocytosis assay, oxLDL uptake assay, lipidomic plasma analysis |
Circulation |
High |
29739755
|
| 2018 |
Chemerin-activated CMKLR1 signaling in inflammatory macrophages is regulated by GRK6-mediated phosphorylation and β-arrestin 2 recruitment: co-expression of GRK6 enhances β-arrestin recruitment to CMKLR1 after chemerin stimulation; GRK6- and β-arrestin 2-deficient macrophages show decreased CMKLR1 internalization, increased migration toward chemerin, and altered AKT and ERK signaling. |
BRET/co-IP β-arrestin recruitment assay, flow cytometry internalization assay, GRK6 KO and β-arrestin 2 KO primary macrophages, migration assay, Western blot (AKT, ERK) |
Molecular immunology |
High |
30576947
|
| 2018 |
Chemerin suppresses HCC metastasis through a CMKLR1-PTEN-Akt signaling axis: chemerin interferes with the PTEN-CMKLR1 protein interaction (shown by immunoprecipitation), upregulates PTEN expression and phosphatase activity, reduces PTEN ubiquitination, and decreases p-Akt (Ser473), thereby suppressing HCC cell migration and invasion. |
Co-immunoprecipitation, forced expression/RNAi, PTEN phosphatase activity assay, ubiquitination assay, Western blot, in vivo mouse metastasis models |
British journal of cancer |
High |
29717200
|
| 2018 |
Chemerin acting via ChemR23 in keratinocytes triggers inflammatory responses through a ROS-sirt1-NF-κB signaling pathway: chemerin increases ROS production, suppresses sirt1 expression and deacetylase activity, leading to increased NF-κB p65 acetylation and activation, and enhanced secretion of inflammatory cytokines. |
ELISA (cytokines), Western blot (NF-κB, sirt1), ROS measurement, in vivo imiquimod mouse psoriasis model |
Journal of cellular biochemistry |
Medium |
30426542
|
| 2019 |
CMKLR1 in vascular smooth muscle cells (VSMCs) acts as a determinant of synthetic and osteoblastic phenotype, promoting phosphate-induced calcification: ChemR23-deficient VSMCs maintain a non-synthetic phenotype and resist phosphate-induced calcification; ChemR23-deficient mice are protected against vitamin D3-induced vascular calcification. Resolvin E1 inhibits VSMC calcification through ChemR23. |
ChemR23 KO mice, primary VSMC isolation, calcification assays, phenotype marker gene expression, in vivo vitamin D3 calcification model, Fat-1 transgene experiments |
Cardiovascular research |
High |
30597013
|
| 2019 |
Chemerin recruits NK cells to the tumor microenvironment via CMKLR1: CMKLR1-/- and chemerin-/- (Rarres2-/-) mice showed impaired tumor-infiltrating NK cells in murine melanoma models, and the NK cell-enhancing and tumor-inhibitory effects of all-trans retinoic acid were completely abrogated in both Rarres2-/- and Cmklr1-/- mice, demonstrating a required chemerin-CMKLR1 axis for NK cell recruitment. |
Chemerin KO and CMKLR1 KO mouse tumor models, flow cytometry of tumor-infiltrating NK cells, atRA treatment |
Immunology |
High |
31063220
|
| 2019 |
Chemerin inhibits vascular calcification through ChemR23 in VSMCs: chemerin reduces phosphate-induced calcification and increases matrix gla protein (MGP) expression in wild-type VSMCs but is devoid of these effects in VSMCs lacking ChemR23. |
Primary VSMC calcification assay, ChemR23 KO VSMCs, MGP expression measurement |
Journal of internal medicine |
Medium |
31197872
|
| 2019 |
ChemR23 (CMKLR1) deficiency in hematopoietic cells reduces atherosclerosis by promoting M2 macrophage polarization, increasing cholesterol efflux, and reducing pDC frequency and their migration to atherosclerotic lesions. ChemR23-deficient pDCs show reduced migratory capacity and decreased CCR7 expression; adoptive transfer confirmed reduced accumulation of ChemR23-KO pDCs in lesions. |
ChemR23 KO/knockin eGFP reporter mice crossed to Apoe-/- mice, bone marrow transplantation (hematopoietic KO), pDC adoptive transfer, histology, flow cytometry, gene expression |
Arteriosclerosis, thrombosis, and vascular biology |
High |
30786742
|
| 2020 |
The chemerin/CMKLR1 axis promotes inflammation and pyroptosis in diabetic cardiomyopathy through NLRP3 inflammasome activation: CMKLR1 siRNA attenuated NLRP3 expression, caspase-1 activation, IL-1β maturation, and pyroptosis in vivo. In vitro, silencing either CMKLR1 or NLRP3 suppressed activated caspase-1, IL-1β, and pyroptosis, and combined silencing further decreased IL-1β and pyroptosis, indicating NLRP3 acts downstream of CMKLR1. |
siRNA knockdown (CMKLR1, NLRP3) in vivo and in vitro, Western blot, LDH/EthD-III cell death assays, cardiac function measurement |
Frontiers in physiology |
Medium |
32390873
|
| 2020 |
Chemerin upregulates PTEN expression/activity and suppresses PD-L1 expression in prostate and sarcoma tumor cells via a CMKLR1/PTEN/PD-L1 signaling cascade: CMKLR1 knockdown abrogated both chemerin-induced PTEN upregulation and PD-L1 suppression; PI3K/AKT/mTOR pathway inhibitors mimicked these effects, and forced chemerin expression in DU145 xenografts increased PTEN and decreased PD-L1 in vivo. |
siRNA knockdown of CMKLR1, Western blot, specific pathway inhibitors, in vivo xenograft model with forced chemerin expression |
Clinical cancer research |
Medium |
32605911
|
| 2020 |
n-3 PUFA-derived resolvin E1 and its receptor ChemR23 constitute a key axis restricting aortic valve stenosis progression: abrogation of ChemR23 enhanced disease progression, and the beneficial effects of endogenous n-3 PUFA synthesis (Fat-1 transgene) were abolished in the absence of ChemR23, establishing a required role for ChemR23 in RvE1-mediated inhibition of valvular calcification. |
ChemR23 KO mice, Fat-1tg × Apoe-/- mice, echocardiography, histology, lipidomics (LC-MS/MS) |
Circulation |
High |
32506925
|
| 2021 |
An agonist anti-ChemR23 monoclonal antibody induces ChemR23 receptor signaling, promotes macrophage efferocytosis, and reduces neutrophil tissue accumulation. In ongoing chronic colitis models, the antibody triggered resolution with decreased tissue lesions, fibrosis, and inflammation-driven tumors, demonstrating that GPCR agonism at ChemR23 is sufficient to drive resolution of chronic inflammation. |
Agonist mAb characterization, efferocytosis assay, neutrophil apoptosis assay, chronic colitis mouse models, transcriptional analysis in IBD patients |
Science advances |
High |
33811066
|
| 2021 |
The chemerin-CMKLR1 axis restricts cold-induced thermogenesis and beige fat formation by dampening cAMP-PKA signaling in adipocytes, thereby reducing IL-33 production from beige adipocytes and interrupting a feed-forward circuit between beige adipocytes and type 2 innate immunity. Adipocyte-specific CMKLR1 deletion enhanced beige fat and thermogenesis and protected against diet-induced obesity. |
Adipocyte-specific CMKLR1 knockout mice, cold exposure experiments, cAMP/PKA signaling assays, IL-33 measurement, type 2 innate immune cell analysis, metabolic phenotyping |
Science immunology |
High |
34330814
|
| 2022 |
The chemerin-CMKLR1 axis in intestinal epithelial cells (IECs) restricts microbiota-driven colonic neutrophilia and tumorigenesis by upregulating lactoperoxidase (LPO): IEC-specific CMKLR1 deletion reduced LPO expression, causing outgrowth of gram-negative bacteria and dysregulated CXCL1/2-mediated neutrophilia; LPO supplementation fully rescued these phenotypes. |
Intestinal epithelial cell-specific CMKLR1 KO mice, LPO expression analysis, microbiome analysis, neutrophil quantification, LPO supplementation rescue experiment |
Proceedings of the National Academy of Sciences of the United States of America |
High |
35858331
|
| 2022 |
Chemerin enhances mesenchymal features of glioblastoma cells through a CMKLR1-dependent mechanism: chemerin suppresses ubiquitin-proteasomal degradation of CMKLR1, thereby enhancing NF-κB pathway activation; this CMKLR1/NF-κB axis also drives M2 polarization of tumor-associated macrophages and their mesenchymal phenotype-promoting ability. α-NETA blockade disrupted this network. |
Co-immunoprecipitation, ubiquitination assay, NF-κB reporter, CMKLR1 overexpression/knockdown, GBM xenograft models, macrophage polarization assays |
Oncogene |
Medium |
35459783
|
| 2023 |
RvE1/ChemR23 ameliorates hypertension and vascular remodeling by activating AMPKα/Nrf2 signaling: RvE1 inhibited Ccl5 expression in VSMCs via AMPKα/Nrf2/canonical NF-κB pathway (reducing immune cell infiltration) and regulated VSMC phenotypic transformation and proliferation. All effects were reversed by ChemR23 knockdown (AAV9-shRNA). |
AAV9-mediated ChemR23 knockdown, Ang II hypertension mouse model, Western blot (AMPKα, Nrf2, NF-κB), blood pressure measurement, histology, qPCR |
Hypertension |
Medium |
37800344
|
| 2024 |
CMKLR1 controls lipid metabolism in clear cell renal cell carcinoma (ccRCC): genetic or pharmacological suppression of CMKLR1 reduced lipid formation and induced apoptosis, ferroptosis, and autophagy. Mechanistically, CMKLR1 suppresses adipose triglyceride lipase (ATGL) and uniquely controls lipid uptake through regulation of sterol regulatory element-binding protein 1c (SREBP1c) and the CD36 scavenger receptor; α-NETA treatment dramatically reduced tumor growth and lipid storage in patient-derived xenograft models. |
Genetic knockdown/knockout and pharmacological inhibition (α-NETA), lipidomic and transcriptomic profiling, patient-derived xenograft models, Western blot for ATGL/SREBP1c/CD36 |
Cancer research |
High |
38640229
|