Affinage

CCRL2

C-C chemokine receptor-like 2 · UniProt O00421

Length
344 aa
Mass
39.5 kDa
Annotated
2026-06-09
56 papers in source corpus 22 papers cited in narrative 21 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CCRL2 is a seven-transmembrane atypical chemokine receptor that binds chemerin with low nanomolar affinity but does not internalize it, activate G proteins (Gαi/Gαo), recruit β-arrestins, or trigger ERK phosphorylation, distinguishing it from the signaling chemerin receptors CMKLR1 and GPR1 (PMID:18794339, PMID:27716822). Rather than scavenging its ligand, CCRL2 concentrates bioactive chemerin at the cell surface and presents it to CMKLR1 on neighboring cells, a mechanism that underlies its physiological functions (PMID:18794339). On vascular endothelium CCRL2 is upregulated by proinflammatory NF-κB and JAK/STAT signaling and supports adhesion and recruitment of CMKLR1+ leukocytes, including NK cells to the lung, with its endothelial expression epigenetically regulated and required for lung tumor immune surveillance via the CCRL2/chemerin/CMKLR1 axis (PMID:22696441, PMID:31484658, PMID:37343073). CCRL2 also acts through direct protein–protein interactions: it constitutively heterodimerizes with CXCR2 to control CXCR2 surface expression and β2-integrin activation in neutrophils (PMID:28743719), interacts with TLR4 on macrophages to retain surface TLR4 and enhance MyD88–NF-κB signaling and antitumor responses (PMID:33846258), and coprecipitates with JAK2 to potentiate JAK2/STAT3/STAT5 phosphorylation in myeloid (MDS/AML) cells (PMID:35179961). Through these activities CCRL2 regulates leukocyte trafficking, inflammation, neoangiogenesis, and tumor progression (PMID:34638484, PMID:20606167), and binds SFRP1 on stromal cells to amplify Wnt-signaling suppression and impair bone healing (PMID:38477792).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 2008 High

    Established CCRL2 as a non-signaling chemerin-binding receptor that, rather than internalizing ligand, presents bioactive chemerin to the functional receptor CMKLR1 — defining its core mechanistic identity.

    Evidence Binding assays and in vivo passive cutaneous anaphylaxis in CCRL2-deficient mice with comparison to silent chemokine receptors

    PMID:18794339

    Open questions at the time
    • Did not resolve the structural basis of chemerin presentation
    • Transfer of chemerin to CMKLR1 not directly visualized in vivo
  2. 2008 Medium

    Probed whether CCRL2 couples to canonical GPCR signaling using a non-chemerin ligand, showing it does not engage Gi proteins or trigger calcium/migration.

    Evidence ERK1/2 Western blot, pertussis toxin treatment, calcium flux and chemotaxis assays in CRAM-expressing pre-B cells stimulated with CCL5

    PMID:18397265

    Open questions at the time
    • PTX-insensitive ERK readout left signaling route ambiguous
    • Single cell-line context
  3. 2009 Medium

    Characterized CCRL2 ligand binding and constitutive trafficking, showing it binds CCL19 yet does not drive migration and recycles via clathrin-coated pits.

    Evidence Radioligand binding, clathrin-mediated recycling, calcium flux and chemotaxis assays in CRAM-expressing cells

    PMID:20002784

    Open questions at the time
    • Physiological relevance of CCL19 binding versus chemerin unclear
    • Single lab
  4. 2010 High

    Defined a cell-intrinsic in vivo role, demonstrating CCRL2 is required for antigen-loaded lung dendritic cell trafficking to lymph nodes and Th2 priming.

    Evidence CCRL2−/− ovalbumin airway inflammation model with adoptive DC transfer and cytokine measurements

    PMID:20606167

    Open questions at the time
    • Molecular mechanism linking CCRL2 to DC migration not defined
    • Ligand dependence not established
  5. 2012 High

    Placed CCRL2 in the endothelial inflammatory program, showing inflammatory induction and chemerin-dependent leukocyte adhesion, and a recruitment defect in vivo.

    Evidence Endothelial stimulation with NF-κB/JAK-STAT inhibitors, in vitro adhesion assays, CCRL2−/− mice in LPS pulmonary inflammation

    PMID:22696441

    Open questions at the time
    • α4β1/VCAM-1 adhesion mechanism downstream of chemerin presentation not fully dissected
  6. 2016 High

    Definitively confirmed CCRL2 as non-signaling by directly testing G protein and β-arrestin coupling against CMKLR1 and GPR1.

    Evidence BRET G protein and β-arrestin recruitment biosensors, ERK phosphorylation, affinity measurements across three receptors

    PMID:27716822

    Open questions at the time
    • Does not address non-canonical or interaction-driven signaling later attributed to CCRL2
  7. 2017 High

    Revealed an interaction-based mechanism: CCRL2 heterodimerizes with CXCR2 to regulate its surface expression and β2-integrin activation, controlling neutrophil recruitment.

    Evidence Reciprocal co-IP, CCRL2−/− inflammatory arthritis models, β2-integrin and CXCR2 surface assays

    PMID:28743719

    Open questions at the time
    • Stoichiometry and structural basis of the heterodimer not resolved
  8. 2017 Medium

    Clarified intracellular handling, showing CCRL2 does not scavenge chemerin and undergoes only weak ligand-independent recycling.

    Evidence Endosomal marker colocalization, scavenging and kinetics comparison versus ACKR3 in transfected and endothelial cells

    PMID:29056935

    Open questions at the time
    • Functional purpose of constitutive recycling unclear
    • Single lab
  9. 2019 High

    Demonstrated that non-hematopoietic (endothelial) CCRL2 mediates lung tumor immune surveillance through the chemerin/CMKLR1 axis driving NK cell infiltration.

    Evidence Ccrl2−/− mice in urethane and KrasG12D/p53 lung tumor models, bone marrow chimeras, adoptive transfer, flow cytometry

    PMID:31484658

    Open questions at the time
    • Endothelial signals controlling CCRL2 expression not yet defined
  10. 2021 High

    Identified a direct CCRL2–TLR4 interaction that retains surface TLR4 and amplifies MyD88-NF-κB signaling, linking CCRL2 to macrophage immunostimulatory activation and antitumor T-cell responses.

    Evidence Co-IP, CCRL2-deficient melanoma models, macrophage and CD8 depletion, TLR4-deficient comparison

    PMID:33846258

    Open questions at the time
    • Whether chemerin binding modulates the TLR4 interaction unknown
  11. 2021 High

    Showed tumor-cell CCRL2 concentrates chemerin to limit neoangiogenesis, with genetic epistasis confirming dependence on chemerin and CMKLR1.

    Evidence DMBA/TPA carcinogenesis, B16/LLC grafts with gain/loss-of-function, epistasis with chemerin−/− and Cmklr1−/−

    PMID:34638484

    Open questions at the time
    • Cell types mediating the anti-angiogenic chemerin/CMKLR1 effect not fully defined
  12. 2021 Medium

    Tested an unexpected function, identifying CCRL2 as an in vitro coreceptor for HIV-2 primary isolates.

    Evidence NP-2/CD4/CCRL2 infection assay with immunofluorescence, proviral DNA PCR, RT activity, syncytia formation

    PMID:33253374

    Open questions at the time
    • No in vivo validation
    • Physiological relevance to HIV infection unestablished
  13. 2022 High

    Extended interaction-based signaling to myeloid malignancy, showing CCRL2 coprecipitates with JAK2 and acts upstream to potentiate JAK2/STAT3/STAT5 phosphorylation.

    Evidence Co-IP, shRNA knockdown in MDS92/MDS-L cells, phospho-Western blots, JAK2V617F epistasis and fedratinib inhibition, xenografts

    PMID:35179961

    Open questions at the time
    • Mechanism by which a non-signaling receptor engages JAK2 not resolved
  14. 2022 Low

    Generated structural hypotheses for the chemerin-binding interface to rationalize how CCRL2 presents chemerin while leaving its C-terminus free for CMKLR1.

    Evidence Protein-protein docking and accelerated molecular dynamics (computational only)

    PMID:35437825 PMID:41380116

    Open questions at the time
    • No experimental validation of predicted hot-spot residues
    • In silico model only
  15. 2023 Medium

    Connected CCRL2 to MDS/sAML epigenetic regulation, showing it modulates DNMT levels and PRC2 pathways and influences azacitidine sensitivity.

    Evidence shRNA knockdown/overexpression in MDS lines, azacitidine sensitivity assays, MDS-L xenograft, pathway analysis

    PMID:36519323

    Open questions at the time
    • Direct molecular link between CCRL2 and DNMT regulation unestablished
    • Single lab
  16. 2023 Medium

    Distinguished CCRL2's ligand-binding function from its heterodimerization effect, showing chemerin-binding neutralization does not block CXCL8/CXCR2 neutrophil responses.

    Evidence SPRm and flow cytometry ligand confirmation, neutralizing antibody, neutrophil degranulation and peritoneal recruitment assays

    PMID:36662882

    Open questions at the time
    • Negative result; does not exclude all chemerin contributions
    • Single lab
  17. 2023 High

    Defined a flow-dependent endothelial mechanism in atherosclerosis where CCRL2-recruited chemerin activates monocyte β2-integrin via chemerin's PDI-like activity independently of CMKLR1.

    Evidence scRNA-seq, CCRL2−/−ApoE−/− mice on high-fat diet, Di-E-GSSG PDI assay, proximity ligation, ERK phosphorylation

    PMID:37279540

    Open questions at the time
    • Generality of CMKLR1-independent chemerin signaling across tissues unclear
  18. 2023 High

    Identified CCRL2 as an alveolar capillary endothelial hallmark gene under epigenetic control whose restoration with 5-Aza enhances NK recruitment and limits lung tumors.

    Evidence scRNA-seq, conditional endothelial CCRL2 KO, chemerin KO, 5-Aza treatment, NK subset flow cytometry, Kras/p53 model

    PMID:37343073

    Open questions at the time
    • Specific epigenetic marks/enzymes controlling CCRL2 not pinpointed
  19. 2024 Medium

    Revealed a stromal Wnt-modulating role through direct CCRL2–SFRP1 binding that suppresses osteogenesis and bone healing in periodontitis.

    Evidence Co-IP/binding assay, Ccrl2-KO mice in extraction socket periodontitis, Wnt pathway and histological analysis

    PMID:38477792

    Open questions at the time
    • Direct effect of CCRL2 on SFRP1 affinity for Wnt ligands not quantified
    • Single lab
  20. 2025 Medium

    Implicated CCRL2 in cell-autonomous IFN-γ/STAT1 signaling in TP53-mutant erythroid AML through JAK2-dependent and -independent STAT1 phosphorylation.

    Evidence CCRL2 KO erythroleukemia lines, proteomics/transcriptomics, STAT1 phospho-assays, JAK2 inhibitor, xenografts (preprint)

    PMID:40060699

    Open questions at the time
    • Not peer-reviewed
    • JAK2-independent route to STAT1 undefined
  21. 2025 Low

    Proposed a cardiac fibrosis function via CCRL2 on macrophages interacting with fibroblast Na+/K+-ATPase to promote fibroblast proliferation.

    Evidence Co-culture, concurrent heart/liver injury mouse model, fibroblast proliferation/migration assays

    PMID:41436601

    Open questions at the time
    • Single binding claim with limited mechanistic follow-up
    • Interaction not validated reciprocally

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a confirmed non-signaling receptor mechanistically couples to JAK2, TLR4, CXCR2, and STAT pathways at the molecular/structural level remains unresolved.
  • No structure of CCRL2 in complex with chemerin or partner receptors
  • Stoichiometry and assembly of CCRL2 heterodimers unknown
  • Mechanism converting ligand presentation into intracellular signaling potentiation undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 3 GO:0060089 molecular transducer activity 2 GO:0001618 virus receptor activity 1
Localization
GO:0005886 plasma membrane 2 GO:0005768 endosome 1
Pathway
R-HSA-168256 Immune System 3 R-HSA-162582 Signal Transduction 2 R-HSA-1643685 Disease 2
Partners
CMKLR1CXCR2JAK2SFRP1TLR4

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2008 CCRL2 binds chemerin as a natural non-signaling ligand without triggering ligand internalization. Instead of internalizing chemerin, CCRL2 increases local concentrations of bioactive chemerin, presenting it to the signaling chemerin receptor CMKLR1 on nearby cells. Binding assays, in vivo passive cutaneous anaphylaxis model with CCRL2-deficient mice, functional comparison with 'silent' chemokine receptors The Journal of experimental medicine High 18794339
2009 CCRL2 (CRAM-B splice variant) binds the homeostatic chemokine CCL19 with affinity similar to CCR7, but unlike CCR7 does not trigger calcium mobilization or cell migration. CCRL2 constitutively recycles via clathrin-coated pits and internalizes CCL19 as well as anti-CRAM antibodies. Radioactive ligand binding assays, clathrin-mediated recycling assays, calcium flux assays, chemotaxis assays in CRAM-expressing cells Immunology Medium 20002784
2012 CCRL2 is upregulated on vascular endothelial cells by proinflammatory stimuli via NF-κB and JAK/STAT signaling pathways. Chemerin binding to CCRL2 on endothelial cells triggers adhesion of CMKLR1+ lymphoid cells through an α4β1 integrin/VCAM-1-dependent mechanism. CCRL2 deficiency elevates plasma chemerin levels and impairs CMKLR1+ NK cell recruitment to airways during LPS-induced inflammation. Endothelial cell culture stimulation assays, NF-κB/JAK/STAT inhibitor experiments, CCRL2−/− mouse models, in vitro adhesion assays, in vivo LPS pulmonary inflammation model Journal of immunology High 22696441
2016 Chemerin binds CCRL2 with low nanomolar affinity but does not activate G proteins (Gαi1, Gαi2, Gαi3, Gαoa, Gαob) or recruit β-arrestin1/2 to CCRL2, in contrast to CMKLR1 and GPR1. CCRL2 also does not promote ERK1/2 phosphorylation upon chemerin binding, confirming it is a non-signaling receptor. BRET-based biosensors for G protein activation, β-arrestin recruitment assays, ERK1/2 phosphorylation assays, binding affinity measurements PloS one High 27716822
2017 CCRL2 constitutively forms homodimers and heterodimers with CXCR2. By heterodimerization with CXCR2, CCRL2 regulates CXCR2 membrane expression and promotes CXCR2-mediated β2-integrin activation. CCRL2-deficient mice show defective neutrophil recruitment and are protected in inflammatory arthritis models. Co-immunoprecipitation and dimerization assays, CCRL2−/− mouse inflammatory arthritis models, β2-integrin activation assays, CXCR2 membrane expression quantification Blood High 28743719
2017 CCRL2 does not internalize or scavenge its ligand chemerin. CCRL2 undergoes weak constitutive, ligand-independent internalization and recycling (slower kinetics than ACKR3 or signaling receptors), colocalizing with EEA1/Rab5-positive early endosomes and Rab11-positive recycling compartments intracellularly. Cell membrane analysis, fluorescence colocalization with endosomal markers, scavenging assays in CCRL2-transfected cells and activated mouse endothelial cells, kinetics comparison Frontiers in immunology Medium 29056935
2019 CCRL2 expressed by non-hematopoietic (endothelial) cells is required for lung tumor immune surveillance. CCRL2 deletion on endothelial cells reduces NK cell infiltration into lungs, promoting tumor progression. This effect is mediated through the CCRL2/chemerin/CMKLR1 axis. Ccrl2−/− mice in urethane-induced and KrasG12D/p53Flox lung tumor models, bone marrow chimeras, adoptive transfer experiments, flow cytometry of tumor infiltrates Cancer immunology research High 31484658
2021 CCRL2 interacts directly with TLR4 on the macrophage cell surface to retain membrane TLR4 expression and enhance downstream MyD88-NF-κB inflammatory signaling, thereby promoting immunostimulatory macrophage activation and antitumor T-cell responses. Co-immunoprecipitation, CCRL2-deficient mouse melanoma models, macrophage depletion experiments, CD8+ T cell depletion, coinjection tumor model, TLR4-deficient mouse comparison Proceedings of the National Academy of Sciences High 33846258
2021 CCRL2 expression by tumor cells can concentrate bioactive chemerin and reduce neoangiogenesis in a manner dependent on the chemerin/CMKLR1 axis. Loss of Ccrl2 accelerated papilloma development in chemical carcinogenesis, while CCRL2 gain-of-function delayed B16 and LLC tumor graft growth; both phenotypes were abrogated by chemerin or Cmklr1 knockout. DMBA/TPA skin carcinogenesis model, B16/LLC tumor graft models with CCRL2 overexpression/knockout, epistasis with chemerin−/− and Cmklr1−/− mice, angiogenesis assays Cancers High 34638484
2022 CCRL2 coprecipitates with JAK2 and potentiates JAK2-STAT interaction. CCRL2 knockdown in MDS92 and MDS-L cells decreases JAK2/STAT3/STAT5 phosphorylation. Erythroleukemia cells expressing JAK2V617F show less effect of CCRL2 knockdown, and fedratinib (JAK2 inhibitor) potentiates the CCRL2 knockdown effect, placing CCRL2 upstream of JAK2/STAT signaling. Co-immunoprecipitation (CCRL2-JAK2), shRNA knockdown, Western blot for phospho-JAK2/STAT3/STAT5, pharmacological JAK2 inhibition, in vivo xenograft models Science advances High 35179961
2023 CCRL2 is expressed as a hallmark of alveolar lung capillary endothelial cells and its expression is epigenetically regulated. Conditional endothelial-targeted ablation of CCRL2 or deletion of chemerin promotes lung tumor progression by reducing recruitment of CD27−CD11b+ mature NK cells. Treatment with 5-aza-2'-deoxycytidine upregulates endothelial CCRL2 expression, increases NK cell recruitment, and reduces lung tumor growth. scRNA-seq of tumor-infiltrating cells, conditional endothelial CCRL2 knockout, chemerin KO, 5-Aza treatment, flow cytometry of NK cell subsets, Kras/p53Flox lung tumor model Cancer immunology research High 37343073
2023 Endothelial CCRL2 induced by disturbed flow recruits chemerin, which activates β2 integrin on monocytes via a protein disulfide isomerase-like enzymatic activity of chemerin (not via monocytic CMKLR1), enhancing ERK1/2 phosphorylation and monocyte adhesion, thereby promoting atherosclerotic plaque formation. CCRL2-/-ApoE-/- mice are protected against plaque formation. scRNA-seq of carotid arteries, CCRL2−/−ApoE−/− double KO mice on high-fat diet, Di-E-GSSG assay for PDI activity, proximity ligation assay for chemerin-β2 integrin interaction, ERK1/2 phosphorylation assays Cardiovascular research High 37279540
2023 CCRL2 knockdown in MDS/sAML cells downregulates DNA methylation and PRC2 activity pathways and increases DNMT suppression by azacitidine. CCRL2 overexpression decreases azacitidine sensitivity. CCRL2 deletion increased azacitidine efficacy in an MDS-L xenograft model, establishing CCRL2 as a modulator of epigenetic regulatory pathways (DNMT levels) in MDS. shRNA knockdown and CCRL2 overexpression in MDS cell lines, in vitro azacitidine sensitivity assays, MDS-L xenograft model, pathway analysis Haematologica Medium 36519323
2024 CCRL2 expressed on LepR+/CAR stromal cells in alveolar bone binds SFRP1 on the cell surface, amplifying SFRP1-mediated suppression of Wnt signaling under inflammatory conditions, thereby inhibiting osteogenic differentiation and impairing extraction socket bone healing in periodontitis. Ccrl2-KO mice show improved bone healing. Co-immunoprecipitation/binding assay for CCRL2-SFRP1 interaction, Ccrl2-KO mouse model with extraction socket periodontitis, Wnt signaling pathway analysis, histological assessment of bone healing Journal of bone and mineral research Medium 38477792
2021 CCRL2 functions as a coreceptor for HIV-2 primary isolates in vitro. NP-2/CD4/CCRL2 cells were infected by HIV-2MIR (and to a lesser extent HIV-1HAN2), as detected by viral antigen immunofluorescence, proviral DNA, reverse transcriptase activity, and syncytia formation. NP-2/CD4/CCRL2 cell infection assay, indirect immunofluorescence, Giemsa staining for syncytia, PCR for proviral DNA, RT activity measurement Briefings in bioinformatics Medium 33253374
2023 CCRL2 antibody-based neutralization of chemerin binding did not attenuate CXCL8-induced human neutrophil degranulation or CXCL8-induced murine neutrophil recruitment to the peritoneum. This negative finding indicates that the ligand-binding function of CCRL2 is dispensable for CXCL8/CXCR2 signaling in neutrophils, suggesting that CCRL2-CXCR2 heterodimerization effects are independent of CCRL2 chemerin-binding capacity. Flow cytometry and Surface Plasmon Resonance microscopy (SPRm) for ligand binding confirmation, neutralizing antibody treatment, human neutrophil degranulation assays, murine peritoneal neutrophil recruitment PloS one Medium 36662882
2025 CCRL2 drives cell-autonomous IFN-γ signaling in AML with erythroid differentiation and TP53 mutations by promoting STAT1 phosphorylation via JAK2-dependent and JAK2-independent mechanisms, independently of exogenous IFN-γ. CCRL2 KO suppresses erythroleukemia growth in vitro and in vivo. CCRL2 KO in erythroleukemia cell lines, proteomics and transcriptomics, STAT1 phosphorylation assays, JAK2 inhibitor experiments, in vivo xenograft models bioRxivpreprint Medium 40060699
2025 CCRL2 expressed on cardiac fibroblast-recruited macrophages facilitates fibroblast proliferation and migration through interaction with Na+/K+-ATPase on fibroblasts, without directly altering the intensity of the inflammatory response. Co-culture assays, concurrent heart/liver injury mouse model, CCRL2 expression characterization, fibroblast proliferation and migration assays Cellular & molecular immunology Low 41436601
2008 CCL5 exposure upregulates CCRL2 (CRAM) surface expression on pre-B cell lines. CCL5 stimulation of CRAM-expressing Nalm6 cells (lacking known CCL5 receptors) induces ERK1/2 phosphorylation that is not inhibited by pertussis toxin, suggesting CRAM does not couple to Gi proteins, and produces no calcium mobilization or migration. Western blot for ERK1/2 phosphorylation, pertussis toxin treatment, calcium flux assay, chemotaxis assay, surface expression by flow cytometry Immunology Medium 18397265
2010 CCRL2 is required for antigen-loaded lung dendritic cell trafficking to mediastinal lymph nodes. CCRL2−/− mice show normal DC recruitment to the lung but defective DC trafficking to lymph nodes, reduced T helper 2 priming, and protection from ovalbumin-induced airway inflammation. Adoptive transfer of CCRL2−/− antigen-loaded DCs into wild-type mice recapitulated the knockout phenotype. CCRL2−/− mouse model, ovalbumin airway inflammation model, adoptive DC transfer, BAL leukocyte counts, cytokine measurements Blood High 20606167
2022 Computational protein-protein docking and accelerated molecular dynamics identified putative hot-spot residues in the CCRL2-chemerin binding interface, with chemerin's β1 strand and CCRL2's extracellular loop 2 as primary interaction regions, and CCRL2 N-terminus/chemerin loop 3 electrostatic interactions stabilizing the complex while leaving the chemerin C-terminus accessible for CMKLR1 engagement. Protein-protein docking, accelerated molecular dynamics, principal component analysis, kernel density estimation Journal of chemical information and modeling (2025 paper) / Proteins (2022 paper) Low 35437825 41380116

Source papers

Stage 0 corpus · 56 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 Mast cell-expressed orphan receptor CCRL2 binds chemerin and is required for optimal induction of IgE-mediated passive cutaneous anaphylaxis. The Journal of experimental medicine 251 18794339
2016 Signaling Properties of Chemerin Receptors CMKLR1, GPR1 and CCRL2. PloS one 146 27716822
2010 Chemokine-like receptor 1 (CMKLR1) and chemokine (C-C motif) receptor-like 2 (CCRL2); two multifunctional receptors with unusual properties. Experimental cell research 138 21056554
2012 Expression, regulation, and function of atypical chemerin receptor CCRL2 on endothelial cells. Journal of immunology (Baltimore, Md. : 1950) 124 22696441
2017 The atypical receptor CCRL2 is required for CXCR2-dependent neutrophil recruitment and tissue damage. Blood 87 28743719
2000 Identification of CRAM, a novel unc-33 gene family protein that associates with CRMP3 and protein-tyrosine kinase(s) in the developing rat brain. The Journal of biological chemistry 84 10851247
2010 Nonredundant role of CCRL2 in lung dendritic cell trafficking. Blood 77 20606167
2021 CCRL2 promotes antitumor T-cell immunity via amplifying TLR4-mediated immunostimulatory macrophage activation. Proceedings of the National Academy of Sciences of the United States of America 59 33846258
2004 Up-regulated expression and activation of the orphan chemokine receptor, CCRL2, in rheumatoid arthritis. Arthritis and rheumatism 56 15188357
2020 Molecular Basis for CCRL2 Regulation of Leukocyte Migration. Frontiers in cell and developmental biology 55 33363177
2009 CCL19 is a specific ligand of the constitutively recycling atypical human chemokine receptor CRAM-B. Immunology 55 20002784
2013 CCRL2, a fringe member of the atypical chemoattractant receptor family. European journal of immunology 40 23580473
2019 The Atypical Receptor CCRL2 Is Essential for Lung Cancer Immune Surveillance. Cancer immunology research 39 31484658
2016 CCRL2 regulates M1/M2 polarization during EAE recovery phase. Journal of leukocyte biology 37 26744451
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
2017 The Atypical Receptor CCRL2 (C-C Chemokine Receptor-Like 2) Does Not Act As a Decoy Receptor in Endothelial Cells. Frontiers in immunology 30 29056935
2023 Endothelial CCRL2 induced by disturbed flow promotes atherosclerosis via chemerin-dependent β2 integrin activation in monocytes. Cardiovascular research 29 37279540
2020 Mycobacterium tuberculosis Heat-Shock Protein 16.3 Induces Macrophage M2 Polarization Through CCRL2/CX3CR1. Inflammation 27 31748849
2008 Human B cells express the orphan chemokine receptor CRAM-A/B in a maturation-stage-dependent and CCL5-modulated manner. Immunology 26 18397265
2012 Elevated chemokine CC-motif receptor-like 2 (CCRL2) promotes cell migration and invasion in glioblastoma. Biochemical and biophysical research communications 23 23142225
2020 The expression of chemerin and its receptors (CMKLR1, GPR1, CCRL2) in the porcine uterus during the oestrous cycle and early pregnancy and in trophoblasts and conceptuses. Animal : an international journal of animal bioscience 21 32398173
2017 Absence of the Non-Signalling Chemerin Receptor CCRL2 Exacerbates Acute Inflammatory Responses In Vivo. Frontiers in immunology 20 29209334
2011 Role of exonic variation in chemokine receptor genes on AIDS: CCRL2 F167Y association with pneumocystis pneumonia. PLoS genetics 20 22046140
2023 CCRL2 affects the sensitivity of myelodysplastic syndrome and secondary acute myeloid leukemia cells to azacitidine. Haematologica 19 36519323
2022 The role of the atypical chemokine receptor CCRL2 in myelodysplastic syndrome and secondary acute myeloid leukemia. Science advances 19 35179961
2020 Expression of chemerin receptors CMKLR1, GPR1 and CCRL2 in the porcine pituitary during the oestrous cycle and early pregnancy and the effect of chemerin on MAPK/Erk1/2, Akt and AMPK signalling pathways. Theriogenology 19 32814246
2015 CRAM-A indicates IFN-γ-associated inflammatory response in breast cancer. Molecular immunology 19 26563945
2020 Ccrl2 deficiency deteriorates obesity and insulin resistance through increasing adipose tissue macrophages infiltration. Genes & diseases 18 35224158
2015 The human chemokine receptor CCRL2 suppresses chemotaxis and invasion by blocking CCL2-induced phosphorylation of p38 MAPK in human breast cancer cells. Medical oncology (Northwood, London, England) 18 26487662
2025 Optogenetic vagal nerve stimulation attenuates heart failure by limiting the generation of monocyte-derived inflammatory CCRL2+ macrophages. Immunity 15 40580954
2021 Expression of CCRL2 Inhibits Tumor Growth by Concentrating Chemerin and Inhibiting Neoangiogenesis. Cancers 15 34638484
2017 Atypical chemokine receptor CCRL2 is overexpressed in prostate cancer cells. Journal of biomedical research 15 29497024
2023 CCRL2 Expression by Specialized Lung Capillary Endothelial Cells Controls NK-cell Homing in Lung Cancer. Cancer immunology research 14 37343073
2024 Leptin receptor (+) stromal cells respond to periodontitis and attenuate alveolar bone repair via CCRL2-mediated Wnt inhibition. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 10 38477792
2022 Exploring CCRL2 chemerin binding using accelerated molecular dynamics. Proteins 10 35437825
2017 Evaluation of chemerin and its receptors, ChemR23 and CCRL2, in gingival tissues with healthy and periodontitis. Odontology 7 28233070
2025 CD160+ intraepithelial lymphocytes and CCRL2+ macrophages drive differential repair in cardiac and liver injuries. Cellular & molecular immunology 6 41436601
2023 Studies with neutralizing antibodies suggest CXCL8-mediated neutrophil activation is independent of C-C motif chemokine receptor-like 2 (CCRL2) ligand binding function. PloS one 6 36662882
2025 Targeting CCRL2 enhances therapeutic outcomes in a tuberculosis mouse model. Frontiers in immunology 5 40181978
2021 CCRL2 Modulates Physiological and Pathological Angiogenesis During Retinal Development. Frontiers in cell and developmental biology 5 35004698
2025 Hirsutella sinensis Fungus Promotes CD8+ T Cell-Mediated Anti-Tumor Immunity by Affecting Tumor-Associated Macrophages-Derived CCRL2. Immunological investigations 3 39819245
2021 C-C Chemokine receptor-like 2 (CCRL2) acts as coreceptor for human immunodeficiency virus-2. Briefings in bioinformatics 3 33253374
2025 CCRL2 promotes the interferon-γ signaling response in myeloid neoplasms with erythroid differentiation and mutated TP53. bioRxiv : the preprint server for biology 2 40060699
2024 Role of CCRL2 in the Pathogenesis of Experimental Autoimmune Myocarditis via P21-Activated Kinase 1/NOD-Like Receptor Protein 3 Pathway. International heart journal 2 38556341
2023 Ccrl2-centred immune-related lncRNA-mRNA co-expression network revealed the local skin immune activation mechanism of moxibustion on adjuvant arthritis mice. Life sciences 2 37406766
2025 A PBD-dimer containing antibody drug conjugate targeting CCRL2 for high-risk MDS/AML. bioRxiv : the preprint server for biology 1 40894621
2024 Neutrophils restricted contribution of CCRL2 genetic variants to COVID-19 severity. Heliyon 1 39811276
2026 A Study on the Association of Ccrl2 Atypical Chemokine Receptor Polymorphism with the Disease Progression of Multiple Sclerosis in Turkish Patients: Insights From a Negative Study. Noro psikiyatri arsivi 0 41777517
2026 A PBD-dimer containing antibody drug conjugate targeting CCRL2 for high-risk MDS/AML including TP53-mutated disease. Blood advances 0 42160756
2026 [Clinical Significance of CCRL2 Regulating Platelet Function in Pediatric Chronic Immune Thrombocytopenia]. Zhongguo shi yan xue ye xue za zhi 0 42227449
2026 Clitocine suppresses TNBC progression by boosting CCRL2 to block survival signals and neutrophil-driven inflammation. Journal of biological engineering 0 42260538
2025 CCRL2 deficiency and dyslipidemia: implications for thrombocytopenia post allo-HSCT. Cytotherapy 0 40183719
2025 Atypical Chemokine Receptor CCRL2 Shapes Tumor Spheroid Structure and Immune Signaling in Melanoma. Biomolecules 0 40867595
2025 A PBD-dimer containing antibody drug conjugate targeting CCRL2 for high-risk MDS/AML. Research square 0 41282192
2025 Multiscale Computational Dissection of CCRL2-Mediated Chemerin Presentation. Journal of chemical information and modeling 0 41380116
2024 Targeting CCRL2 enhances therapeutic outcomes in a tuberculosis mouse model. bioRxiv : the preprint server for biology 0 39386470

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