Affinage

CD200R1

Cell surface glycoprotein CD200 receptor 1 · UniProt Q8TD46

Length
348 aa
Mass
39.0 kDa
Annotated
2026-06-09
100 papers in source corpus 25 papers cited in narrative 25 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CD200R1 is an inhibitory immunoreceptor on myeloid and other immune cells that, upon engagement by its ligand CD200, dampens inflammatory and effector responses (PMID:17667818, PMID:40461553). Ligand binding triggers Src-family-kinase-mediated phosphorylation of the cytoplasmic tail at Y286 and Y297, which recruits the inhibitory adaptors Dok1/Dok2 to suppress Ras/MAPK signaling (PMID:16330532); the receptor relies on N-glycosylation at Asn44 for CD200 binding (PMID:30574022). Through this axis CD200R1 restrains microglial activation via Dok1 (PMID:28792282), limits LPS-induced TNF-α and alloreactivity in vivo (PMID:17667818), and inhibits macrophage phagocytosis through the kinase Csk rather than the SHP phosphatases used by SIRPα, thereby supporting an immunosuppressive tumor-associated macrophage phenotype induced by IL-4 (PMID:40461553). CD200R1 signaling is not uniformly inhibitory: type I interferon induces cleavage of the downstream effector p120-RasGAP, rewiring the receptor from inhibitory to proinflammatory for TLR7/8-induced IFN-γ (PMID:34637328); in macrophages CD200R1 licenses TLR2 pro-inflammatory signaling and inflammasome assembly and supports HSV-1 replication (PMID:23082204); in neutrophils it drives ROS production to limit bacterial colonization (PMID:31073183); and in ILC3s it promotes STAT3 activation and IL-17 production (PMID:36623588). Receptor abundance is tightly controlled: C/EBPβ together with HDAC1 represses CD200R1 transcription under inflammatory and stress conditions (PMID:22776069, PMID:29104062), miR-129-5p represses it posttranscriptionally (PMID:34952004), stress-induced glucocorticoids downregulate it (PMID:31078691), and PPAR-γ activation preserves its expression (PMID:24639050). The CD200–CD200R1 axis additionally governs osteoclastogenesis through the RANKL/NF-κB/MAPK pathway downstream of RANK (PMID:17726108, PMID:23940819). Beyond CD200, the gastrointestinal secretory-cell homologues iSEC1/iSEC2 are CD200R1-selective ligands that suppress intraepithelial lymphocyte function (PMID:27819346).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2004 Medium

    Establishing that the secreted CD200 ectodomain physically engages a family of cell-surface CD200R isoforms defined which receptor (CD200R1) transduces immunomodulation.

    Evidence FACS binding of FITC-CD200Fc to transfected COS7 cells plus isoform-specific mAb functional assays and cloning of CD200R1–R4

    PMID:15187158 PMID:15274657

    Open questions at the time
    • Binding affinities and structural basis of the CD200–CD200R1 interface not defined
    • Functional divergence among R2/R3 isoforms left unresolved
  2. 2005 High

    Identifying Y286/Y297 phosphorylation and Dok1/Dok2 recruitment defined the proximal inhibitory signaling machinery distinguishing CD200R1 from ITIM-bearing receptors.

    Evidence Site-directed tyrosine mutagenesis with mast cell activation readouts

    PMID:16330532

    Open questions at the time
    • Which Src-family kinase phosphorylates the receptor in vivo not specified
    • Link to downstream RasGAP not yet established in this work
  3. 2007 High

    Genetic knockout proved the CD200:CD200R1 interaction is required for suppression of inflammatory cytokine output and alloreactivity in vivo, moving the receptor from correlation to causation.

    Evidence CD200R1−/− mice with TNF-α ELISA, mixed leukocyte culture, and skin graft rejection

    PMID:17667818

    Open questions at the time
    • Cell-type-specific contributions only partially dissected
    • Downstream signaling in knockout not profiled
  4. 2007 High

    Demonstrating CD200R engagement is required for macrophage fusion and osteoclast differentiation extended the receptor's role beyond immune suppression into bone biology.

    Evidence shRNA silencing, soluble receptor ectodomain, and CD200−/− mice with in vitro differentiation and IHC

    PMID:17726108

    Open questions at the time
    • Precise intracellular signaling linking CD200R1 to RANK-driven NF-κB/MAPK not resolved here
  5. 2013 Medium

    Soluble CD200 inhibition of osteoclast differentiation via the RANKL pathway clarified that the axis modulates OSCAR/NFATc1 induction during osteoclastogenesis.

    Evidence In vitro osteoclast differentiation with soluble CD200 and RANKL-pathway gene expression; MSC co-culture; earlier OPG:RANKL modulation in osteoblast cultures

    PMID:16530849 PMID:23940819

    Open questions at the time
    • Apparent opposing effects on osteoclast formation across studies not mechanistically reconciled
    • Direct receptor-proximal signaling not assayed
  6. 2012 High

    Defining transcriptional (C/EBPβ-HDAC1) and posttranscriptional (miR-129-5p) repression explained how inflammatory stimuli lower CD200R1 to release the inhibitory brake.

    Evidence C/EBPβ-KO mice, ChIP, co-IP, HDAC inhibitors, and miR-129-5p 3'-UTR targeting with anti-miR rescue in microglia

    PMID:22776069 PMID:34952004

    Open questions at the time
    • Integration of transcriptional and miRNA control into a single regulatory circuit not tested
    • Stimulus specificity of each mechanism incompletely mapped
  7. 2012 High

    The unexpected finding that CD200R1 is required for TLR2 pro-inflammatory signaling and HSV-1 replication revealed the receptor can act non-inhibitorily depending on context.

    Evidence CD200R1−/− macrophages, cytokine ELISA, inflammasome and TLR2 expression assays, HSV-1 infection model

    PMID:23082204

    Open questions at the time
    • Molecular mechanism by which CD200R1 licenses TLR2 not defined
    • Relationship to canonical Dok/RasGAP signaling unknown
  8. 2016 Medium

    Discovery of CD200R1-selective ligands iSEC1/iSEC2 and a STAT3-promoting role in ILC3s showed the receptor has tissue-specific ligands and context-dependent, even pro-inflammatory, outputs.

    Evidence iSEC1/iSEC2 binding specificity and IEL suppression assays; CD200R1-deficient mice in psoriasis with STAT3 phosphorylation readout; cathepsin K induction in tumor myeloid cells

    PMID:27819346 PMID:34183355 PMID:36623588

    Open questions at the time
    • Signaling distinction between inhibitory and STAT3-promoting outputs not resolved
    • How alternative ligands engage shared cytoplasmic machinery unknown
  9. 2019 High

    Identifying CD200R1-driven neutrophil ROS production as antibacterial established a protective, effector-promoting function in a defined infection.

    Evidence CD200R1−/− mice, F. tularensis infection, ROS assays, and neutrophil-niche depletion rescue

    PMID:31073183

    Open questions at the time
    • Receptor-proximal signaling driving ROS not mapped
    • Ligand engaged in this setting not identified
  10. 2021 Medium

    Showing type I IFN cleaves p120-RasGAP to convert CD200R1 from inhibitory to proinflammatory provided a molecular switch explaining context-dependent receptor output and a link to SLE.

    Evidence IFN-α-treated human PBMCs, Western blot for cleaved p120-RasGAP and rpS6, TLR7/8-induced IFN-γ, SLE patient samples

    PMID:34637328

    Open questions at the time
    • Protease responsible for p120-RasGAP cleavage not identified
    • Causal contribution to SLE pathology not established
  11. 2025 High

    Defining Csk (not SHP-1/SHP-2) as the effector kinase for CD200R1-mediated inhibition of phagocytosis distinguished its mechanism from SIRPα and rationalized combination blockade.

    Evidence CD200R1-deficient mice/macrophages, CD200-KO tumor cells, phagocytosis assays, Csk-vs-SHP signaling analysis, IL-4 induction, and combination with anti-CD47/SIRPα

    PMID:40461553

    Open questions at the time
    • Direct biochemical link between phosphorylated CD200R1 and Csk recruitment not detailed
    • How Csk integrates with Dok/RasGAP axis unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single receptor and its conserved Y286/Y297-Dok-RasGAP module produces opposite (inhibitory vs proinflammatory/STAT3-promoting) outputs across myeloid cells, neutrophils, and ILC3s remains unresolved.
  • No unified model connecting Csk, Dok/RasGAP, p120-RasGAP cleavage, and STAT3 outputs
  • Structural basis of ligand-selective signaling (CD200 vs iSEC1/2) unknown
  • Cell-intrinsic determinants of inhibitory-versus-activating output undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 3 GO:0098772 molecular function regulator activity 3 GO:0060090 molecular adaptor activity 1
Localization
GO:0005886 plasma membrane 2
Pathway
R-HSA-168256 Immune System 4 R-HSA-162582 Signal Transduction 2
Partners
CD200CSKDOK1DOK2ISEC1ISEC2RASA1

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 CD200R1 cytoplasmic tail tyrosine residues Y286 and Y297 are the major phosphorylation sites required for CD200R-mediated inhibition of mast cell activation; Y289 is dispensable. Src family kinase mediates phosphorylation of CD200R and Dok. Phosphorylated CD200R recruits inhibitory adaptor proteins Dok1 and Dok2, leading to inhibition of Ras/MAPK activation. Site-directed mutagenesis of tyrosine residues, in vitro mast cell activation assays Journal of leukocyte biology High 16330532
2004 CD200Fc (extracellular domain of CD200) physically binds to each of the CD200R isoforms (CD200R1–R4) expressed on the cell surface, as shown by FACS with FITC-labeled CD200Fc on transfected COS7 cells. Anti-CD200R1/R4 mAbs elicit immunomodulatory responses comparable to CD200Fc (suppressing CTL and IL-2/IL-4), while anti-CD200R2/R3 show significantly lesser effects. FACS binding assay with FITC-labeled CD200Fc on transfected COS7 cells; functional assays with mAbs Journal of immunology Medium 15187158
2004 A family of CD200R isoforms (CD200R1–R4) was identified on mouse chromosome 16 juxtaposed to the CD200 gene. The isoforms show distinct tissue and cell-type expression patterns. Anti-CD200R1/R4 mAbs modulate allogeneic mixed-lymphocyte responses comparably to CD200Fc, whereas anti-CD200R2/R3 show different functional effects. CD200Fc physically interacts with each CD200R isoform on the cell surface. 5'-RACE, cDNA and genomic DNA cloning, Northern blot, RT-PCR, FACS with rabbit polyclonal and rat monoclonal antibodies, mixed-lymphocyte response assays American journal of reproductive immunology Medium 15274657
2007 CD200R1 knockout mice show that the CD200:CD200R1 interaction is required for suppression of LPS-induced splenic TNF-α production and for CD200Fc-mediated suppression of mixed leukocyte culture alloreactivity. CD200R1 on both antigen-presenting cells and T responder cells contributes to maximal immunoregulation. CD200Fc fails to suppress graft rejection in CD200R1−/− mice. CD200R1 knockout mice generated by ES cell transformation; FACS, ELISA for TNF-α, mixed leukocyte culture, skin graft rejection model Transplantation High 17667818
2007 CD200R (expressed on myeloid cells including osteoclast precursors) engagement by CD200 (expressed on macrophages at onset of fusion) is required for macrophage fusion and osteoclast differentiation. CD200R knockdown by shRNA or addition of soluble CD200R extracellular domain prevents macrophage fusion. CD200−/− mice have fewer osteoclasts and more bone, consistent with CD200-CD200R controlling osteoclastogenesis via NF-κB and MAPK pathways downstream of RANK. shRNA silencing of CD200R, soluble recombinant CD200R extracellular domain addition, CD200−/− mice, in vitro differentiation assays, immunohistochemistry Proceedings of the National Academy of Sciences of the United States of America High 17726108
2012 CD200R1 signaling inhibits microglial activation downstream via the Dok1 pathway. CD200Fc treatment after germinal matrix hemorrhage increased Dok1 expression and decreased IL-1β and TNF-α; these effects were abolished by CD200R1 siRNA and Dok1 siRNA, identifying a CD200R1/Dok1 signaling axis. siRNA knockdown of CD200R1 and Dok1, Western blot, CD200Fc treatment in rat GMH model Journal of cerebral blood flow and metabolism Medium 28792282
2012 CD200R1 expression in microglia is negatively regulated by the transcription factor C/EBPβ: LPS-induced decrease in CD200R1 mRNA/protein is absent in C/EBPβ-deficient mice; C/EBPβ overexpression in BV2 cells reduces basal CD200R1 expression. C/EBPβ binds the CD200R1 promoter in LPS-treated glial cells. HDAC1 co-immunoprecipitates with C/EBPβ and binds the CD200R1 promoter region, and HDAC1 inhibitors reverse LPS-induced CD200R1 downregulation. Primary microglial cultures from WT and C/EBPβ-KO mice, C/EBPβ overexpression in BV2 cells, qChIP, co-immunoprecipitation, HDAC inhibitor treatment, qRT-PCR, Western blot Journal of neuroinflammation High 22776069
2014 PPAR-γ activation by the endogenous ligand 15d-PGJ2 prevents LPS/IFN-γ-induced downregulation of CD200R1 in reactive microglial cells and upregulation of CD200 in astrocytes. PPAR-γ-mediated neuroprotection in neuron-microglia co-cultures depends on CD200-CD200R1 interaction, as blocking this interaction abolishes the neuroprotective effect. Primary neuronal and glial cultures, neuron-microglia co-cultures, PPAR-γ agonist treatment, CD200-CD200R1 blocking, qRT-PCR, Western blot Glia Medium 24639050
2012 CD200R1 expression in microglia is regulated posttranscriptionally by miR-129-5p, which binds the 3'-UTR of CD200R1 mRNA and shuttles it to cytoplasmic processing bodies. Arsenic demethylates the miR-129-5p promoter, increasing its expression and repressing CD200R1. Anti-miR-129 in vivo reversed CD200R1 downregulation and reduced IL-6 and TNF-α. A miR-129-5p→CD200R1→IL-6/TNF-α axis was confirmed by CD200R1 siRNA loss-of-function. In silico analysis, primary neonatal microglia and BV2 cells, stereotaxic anti-miR injection in mice, CD200R1 siRNA, qRT-PCR, promoter methylation analysis The Journal of biological chemistry Medium 34952004
2018 N-glycosylation of CD200R1 at asparagine 44 (Asn44) is required for CD200-CD200R1 interaction; mutation of this site disrupts CD200 binding and upregulates proinflammatory markers (iNOS, CD86, IL-1β, TNF-α) in a neuronal-microglia co-culture system. Site-directed mutagenesis of glycosylation site, neuronal-microglia co-culture, cytokine measurement, binding assay Journal of inflammation Medium 30574022
2021 Type I interferon (IFN-α) rewires CD200R1 signaling from inhibitory to proinflammatory by inducing cleavage of p120-RasGAP, a downstream effector of CD200R1. In the presence of cleaved p120-RasGAP, CD200R loses its capacity to inhibit rpS6 phosphorylation (mTORC1). After IFN-α pretreatment, CD200R switches from inhibiting to potentiating TLR7/8-induced IFN-γ expression. SLE patient PBMCs have increased cleaved p120-RasGAP and altered CD200R function. Human PBMC treatment with IFN-α, Western blot for cleaved p120-RasGAP and rpS6 phosphorylation, cytokine measurement, patient samples from SLE Science signaling Medium 34637328
2012 CD200R1 is required for TLR2-mediated pro-inflammatory signaling in macrophages: CD200R1−/− peritoneal macrophages show 70–75% reduction in IL-6 and CCL5 in response to TLR2 agonist Pam2CSK4 and HSV-1. CD200R1−/− macrophages cannot upregulate TLR2 or assemble a functional inflammasome in response to HSV-1. CD200R1−/− mice are protected from HSV-1 infection, and CD200R1−/− fibroblasts and macrophages show reduced ability to support HSV-1 replication. CD200R1−/− mice, ex vivo macrophage assays, ELISA for cytokines, HSV-1 infection model, TLR2 expression assay PloS one High 23082204
2016 CD200R engagement on ILC3s promotes IL-17A production by enhancing STAT3 activation, contrary to its inhibitory role in myeloid cells. CD200R1-deficient mice show reduced psoriasis severity due to reduced IL-17 production, identifying a cell-intrinsic role of CD200R1 on ILC3s. CD200R1-deficient mice, psoriasis models, cytokine production assays, STAT3 phosphorylation analysis Mucosal immunology Medium 36623588
2019 CD200R1 deletion in mice leads to increased bacterial burden in neutrophils after Francisella tularensis infection. CD200R1-deficient neutrophils have significantly reduced reactive oxygen species (ROS) production, indicating CD200R1-mediated ROS production in neutrophils limits bacterial colonization. Depletion of the neutrophil niche in CD200R1−/− mice restores infection to wild-type levels. CD200R1−/− mice, in vivo F. tularensis infection, ROS assay, neutrophil depletion, bacterial burden quantification Nature communications High 31073183
2017 Stress-induced reduction of CD200R expression in hippocampal microglia primes neuroinflammatory responses. CAAT/Enhancer Binding Protein β (C/EBPβ) is induced by stress and inversely associated with CD200R expression. Intracisterna magna administration of soluble CD200 (mCD200Fc) blocked stress-induced microglial priming, and mCD200R1Fc recapitulated the priming effect. CD200Fc also blocked stress-induced hippocampal HMGB1 increase. In vivo stressor exposure (inescapable tailshock), intracisterna magna injection of mCD200Fc or mCD200R1Fc, ex vivo microglial assays, qRT-PCR for CD200R and C/EBPβ, HMGB1 measurement Brain, behavior, and immunity Medium 29104062
2019 Glucocorticoids mediate stress-induced reduction of CD200R1 in microglia: pharmacological GC receptor blockade (RU486) and adrenalectomy mitigated stress-induced CD200R1 downregulation; exogenous corticosterone reduced CD200R1 expression in vivo and in primary microglia in vitro, indicating direct GC action on microglia. Pharmacological blockade (RU486), adrenalectomy, exogenous CORT administration, primary microglia culture, qRT-PCR and protein expression Brain, behavior, and immunity Medium 31078691
2014 DNA aptamers binding murine CD200R1 act as agonists in the absence of CD200, inducing rapid phosphorylation of the CD200R1 cytoplasmic tail and initiating immune inhibitory signaling. They suppress CTL induction in allogeneic mixed leukocyte culture. Suppression is abolished with CD200R1−/− responder cells, confirming CD200R1-dependent mechanism. PEGylated aptamers enhance allogeneic skin graft survival comparably to CD200Fc in vivo. DNA aptamer SELEX, CD200R1 phosphorylation assay, mixed leukocyte culture CTL assay, CD200R1−/− cells as controls, in vivo skin graft model Molecular therapy. Nucleic acids Medium 25158092
2017 A CD200R-CD28 fusion protein (immunomodulatory fusion protein, IFP) converts CD200R inhibitory signaling into CD28 costimulatory signaling in CD8+ T cells. IFPs containing a dimerizing motif and predicted tumor-T cell distance for immunological synapse localization provide strongest costimulation. T cells transduced with CD200R-CD28 IFP show enhanced proliferation and effector function against CD200+ leukemic cells and eradicate disseminated leukemia in vivo more efficiently than wild-type T cells. Fusion protein engineering, in vitro T cell proliferation and cytokine assays, adoptive transfer in disseminated leukemia mouse model, human primary T cell transduction Blood Medium 29042364
2025 CD200R1 inhibits macrophage phagocytosis via the kinase Csk (not SHP-1/SHP-2 as used by SIRPα). Blocking or removing CD200R1 from macrophages or CD200 from tumor cells increases phagocytosis and suppresses tumor growth. In humans, CD200R1 is mainly expressed on immunosuppressive macrophages and is induced by IL-4. Combined blockade of CD200R1-CD200 and SIRPα-CD47 further boosts phagocytosis beyond either alone. CD200R1-deficient mice and macrophages, CD200 knockout tumor cells, phagocytosis assays, signaling pathway analysis (Csk vs SHP), IL-4 induction experiments, tumor growth models Nature communications High 40461553
2023 A humanized effectorless IgG1 antibody (23ME-00610) against CD200R1 binds human CD200R1 with high affinity (KD <0.1 nM), blocks CD200 binding, and inhibits recruitment of the downstream adaptor DOK2. It induces T-cell cytokine production and enhances T cell-mediated tumor cell killing in vitro and inhibits tumor growth in vivo. Antibody binding assay (KD measurement), CD200 competition assay, DOK2 recruitment assay, T cell cytokine and killing assays, in vivo tumor model Oncoimmunology Medium 37288324
2016 CD200R engagement on CD200R+ myeloid cells within CD200+ squamous cell carcinomas induces expression of cathepsin K (Ctsk), which promotes tumor cell migration and metastasis. Ctsk induction depends on CD200-CD200R axis engagement (shown in coculture system). Ctsk inhibition blocks cSCC migration in vitro, and CD200 disruption reduces metastasis in vivo. RNA sequencing of CD11B+CD200R+ cells, CD200R+ myeloid-cSCC coculture, Ctsk inhibition assays, CD200 disruption in tumor cells, in vivo metastasis model Cancer research Medium 34183355
2008 Antibody-mediated blockade of CD200R1 in vivo aggravates experimental autoimmune encephalomyelitis (EAE) clinical course, with augmented T cell and activated iNOS+ macrophage infiltration. In vitro blockade of CD200R on macrophages co-cultured with CD200-expressing hippocampal neurons enhances IFN-γ-induced IL-6 release and neuronal cell death. Anti-CD200R blocking antibody in vivo (EAE model), co-culture of macrophages and neurons with CD200R blockade, cytokine ELISA, immunohistochemistry Journal of neuroimmunology Medium 18164423
2013 Soluble CD200 inhibits osteoclast differentiation from precursors and their maturation into bone-resorbing cells in vitro by inhibiting the RANKL signaling pathway and gene expression of osteoclast markers OSCAR and NFATc1. MSC-mediated inhibition of osteoclast formation depends on cell-cell contact and is associated with CD200 expression on MSC surface (engaging CD200R on osteoclast precursors). In vitro osteoclast differentiation assay, soluble CD200 addition, gene expression analysis (RANKL pathway, OSCAR, NFATc1), MSC-osteoclast co-culture with CD200 expression correlation PloS one Medium 23940819
2006 CD200:CD200R1 interaction alters OPG:RANKL ratios to modulate bone formation: CD200Fc or endogenous CD200 overexpression in osteoblast precursors increases OPG:RANKL ratios and bone nodule growth in culture, while anti-CD200 abolishes this effect. Real-time PCR for OPG/RANKL mRNA, bone nodule quantification, CD200-overexpressing transgenic mouse calvariae, CD200Fc and anti-CD200 mAb treatments Immunology letters Medium 16530849
2016 Novel CD200 homologues iSEC1 and iSEC2, expressed exclusively by gastrointestinal secretory cells, bind CD200R1 (but not other CD200R family members). Binding of iSEC1 to CD200R on intraepithelial lymphocytes suppresses their cytokine production and cytolytic activity. Binding assay (iSEC1/iSEC2 to CD200R family members), IEL cytokine production and cytolysis assay after iSEC1 treatment Scientific reports Medium 27819346

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 Distribution of the immune inhibitory molecules CD200 and CD200R in the normal central nervous system and multiple sclerosis lesions suggests neuron-glia and glia-glia interactions. Journal of neuropathology and experimental neurology 159 19151626
2011 CD200-CD200R dysfunction exacerbates microglial activation and dopaminergic neurodegeneration in a rat model of Parkinson's disease. Journal of neuroinflammation 115 22053982
2004 CD200 is a ligand for all members of the CD200R family of immunoregulatory molecules. Journal of immunology (Baltimore, Md. : 1950) 111 15187158
2007 The inhibitory CD200R is differentially expressed on human and mouse T and B lymphocytes. Molecular immunology 110 17714785
2012 CD200-CD200R1 interaction contributes to neuroprotective effects of anandamide on experimentally induced inflammation. Glia 104 22653796
2018 Role of the CD200-CD200R Axis During Homeostasis and Neuroinflammation. Neuroscience 95 30367946
2021 CD200:CD200R Interactions and Their Importance in Immunoregulation. International journal of molecular sciences 94 33562512
2011 Impaired CD200-CD200R-mediated microglia silencing enhances midbrain dopaminergic neurodegeneration: roles of aging, superoxide, NADPH oxidase, and p38 MAPK. Free radical biology & medicine 83 21295135
2012 CD200R signaling in tumor tolerance and inflammation: A tricky balance. Current opinion in immunology 76 22264927
2008 CNS inflammation and neuronal degeneration is aggravated by impaired CD200-CD200R-mediated macrophage silencing. Journal of neuroimmunology 75 18164423
2014 The CD200-CD200R1 inhibitory signaling pathway: immune regulation and host-pathogen interactions. Advances in immunology 73 24388216
2010 CD200R1 agonist attenuates mechanisms of chronic disease in a murine model of multiple sclerosis. The Journal of neuroscience : the official journal of the Society for Neuroscience 71 20147531
2007 Mice lacking CD200R1 show absence of suppression of lipopolysaccharide-induced tumor necrosis factor-alpha and mixed leukocyte culture responses by CD200. Transplantation 68 17667818
2011 CD200-CD200R signaling suppresses anti-tumor responses independently of CD200 expression on the tumor. Oncogene 64 22020332
2017 Stress disinhibits microglia via down-regulation of CD200R: A mechanism of neuroinflammatory priming. Brain, behavior, and immunity 63 29104062
2014 Brain innate immunity in the regulation of neuroinflammation: therapeutic strategies by modulating CD200-CD200R interaction involve the cannabinoid system. Current pharmaceutical design 63 24588829
2012 Characterization and functionality of the CD200-CD200R system during mesenchymal stromal cell interactions with T-lymphocytes. Immunology letters 63 22575528
2007 CD200 and its receptor, CD200R, modulate bone mass via the differentiation of osteoclasts. Proceedings of the National Academy of Sciences of the United States of America 62 17726108
2020 The CD200/CD200R signaling pathway contributes to spontaneous functional recovery by enhancing synaptic plasticity after stroke. Journal of neuroinflammation 58 32473633
2005 Augmented Induction of CD4+CD25+ Treg using monoclonal antibodies to CD200R. Transplantation 58 15880066
2002 Anti-CD200R ameliorates collagen-induced arthritis in mice. Clinical immunology (Orlando, Fla.) 57 12217336
2020 CD200-CD200R Pathway in the Regulation of Tumor Immune Microenvironment and Immunotherapy. Advances in experimental medicine and biology 56 32030689
2012 CD200/CD200R paired potent inhibitory molecules regulating immune and inflammatory responses; Part I: CD200/CD200R structure, activation, and function. Acta medica (Hradec Kralove) 56 22696929
2007 CD200-CD200R regulation of microglia activation in the pathogenesis of Parkinson's disease. Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology 53 18040859
2017 Monocytes, microglia, and CD200-CD200R1 signaling are essential in the transmission of inflammation from the periphery to the central nervous system. Journal of neurochemistry 52 28164283
2017 A CD200R-CD28 fusion protein appropriates an inhibitory signal to enhance T-cell function and therapy of murine leukemia. Blood 52 29042364
2005 Identification of tyrosine residues crucial for CD200R-mediated inhibition of mast cell activation. Journal of leukocyte biology 49 16330532
2012 The immune inhibitory complex CD200/CD200R is developmentally regulated in the mouse brain. The Journal of comparative neurology 48 22323214
2004 Structural and functional heterogeneity in the CD200R family of immunoregulatory molecules and their expression at the feto-maternal interface. American journal of reproductive immunology (New York, N.Y. : 1989) 48 15274657
2014 CD200R1 and CD200 expression are regulated by PPAR-γ in activated glial cells. Glia 47 24639050
2008 CD200R surface expression as a marker of murine basophil activation. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology 47 19134017
2021 CD200-CD200R immune checkpoint engagement regulates ILC2 effector function and ameliorates lung inflammation in asthma. Nature communications 46 33953190
2020 The prenatal challenge with lipopolysaccharide and polyinosinic:polycytidylic acid disrupts CX3CL1-CX3CR1 and CD200-CD200R signalling in the brains of male rat offspring: a link to schizophrenia-like behaviours. Journal of neuroinflammation 46 32829711
2016 CD200R1 agonist attenuates glial activation, inflammatory reactions, and hypersensitivity immediately after its intrathecal application in a rat neuropathic pain model. Journal of neuroinflammation 46 26891688
2005 Augmented induction of CD4+CD25+ Treg using monoclonal antibodies to CD200R. Transplantation 44 15729177
2020 Disease Progression-Dependent Expression of CD200R1 and CX3CR1 in Mouse Models of Parkinson's Disease. Aging and disease 42 32257540
2012 Inhibition of CD200R1 expression by C/EBP β in reactive microglial cells. Journal of neuroinflammation 42 22776069
2019 CD200-CD200R1 inhibitory signaling prevents spontaneous bacterial infection and promotes resolution of neuroinflammation and recovery after stroke. Journal of neuroinflammation 41 30777093
2023 Dysregulated CD200-CD200R signaling in early diabetes modulates microglia-mediated retinopathy. Proceedings of the National Academy of Sciences of the United States of America 38 37903272
2012 Chronic infection drives expression of the inhibitory receptor CD200R, and its ligand CD200, by mouse and human CD4 T cells. PloS one 36 22496920
2004 Induction of tolerance-inducing antigen-presenting cells in bone marrow cultures in vitro using monoclonal antibodies to CD200R. Transplantation 36 15114074
2018 CD200 modulates spinal cord injury neuroinflammation and outcome through CD200R1. Brain, behavior, and immunity 35 29870752
2012 Aberrant CD200/CD200R1 expression and function in systemic lupus erythematosus contributes to abnormal T-cell responsiveness and dendritic cell activity. Arthritis research & therapy 34 22621248
2015 CD200R1 agonist attenuates LPS-induced inflammatory response in human renal proximal tubular epithelial cells by regulating TLR4-MyD88-TAK1-mediated NF-κB and MAPK pathway. Biochemical and biophysical research communications 33 25791482
2014 Decreased CD200R expression on monocyte-derived macrophages correlates with Th17/Treg imbalance and disease activity in rheumatoid arthritis patients. Inflammation research : official journal of the European Histamine Research Society ... [et al.] 33 24496593
2017 The immunoglobulin superfamily member CD200R identifies cells involved in type 2 immune responses. Allergy 32 28106273
2016 A Critical Role for CD200R Signaling in Limiting the Growth and Metastasis of CD200+ Melanoma. Journal of immunology (Baltimore, Md. : 1950) 31 27385779
2015 Reduced Dendritic Cells Expressing CD200R1 in Children with Inflammatory Bowel Disease: Correlation with Th17 and Regulatory T Cells. International journal of molecular sciences 31 26690123
2017 Gingival Tissue Inflammation Promotes Increased Matrix Metalloproteinase-12 Production by CD200Rlow Monocyte-Derived Cells in Periodontitis. Journal of immunology (Baltimore, Md. : 1950) 30 29101312
2013 CD200R/CD200 inhibits osteoclastogenesis: new mechanism of osteoclast control by mesenchymal stem cells in human. PloS one 30 23940819
2018 CD200-CD200R imbalance correlates with microglia and pro-inflammatory activation in rat spinal cords exposed to amniotic fluid in retinoic acid-induced spina bifida. Scientific reports 29 30006626
2021 The CD200R1 microglial inhibitory receptor as a therapeutic target in the MPTP model of Parkinson's disease. Journal of neuroinflammation 28 33823877
2020 Maternal Immune Activation Sensitizes Male Offspring Rats to Lipopolysaccharide-Induced Microglial Deficits Involving the Dysfunction of CD200-CD200R and CX3CL1-CX3CR1 Systems. Cells 28 32664639
2019 Neurogenesis promoted by the CD200/CD200R signaling pathway following treadmill exercise enhances post-stroke functional recovery in rats. Brain, behavior, and immunity 28 31513876
2013 The role of CD200-CD200R in tumor immune evasion. Journal of theoretical biology 27 23541619
2021 The CD200-CD200R Axis Promotes Squamous Cell Carcinoma Metastasis via Regulation of Cathepsin K. Cancer research 26 34183355
2019 CD200R deletion promotes a neutrophil niche for Francisella tularensis and increases infectious burden and mortality. Nature communications 26 31073183
2019 CD200-CD200R signaling and diseases: a potential therapeutic target? International journal of physiology, pathophysiology and pharmacology 26 31993106
2018 Antitumor Activity of TLR7 Is Potentiated by CD200R Antibody Leading to Changes in the Tumor Microenvironment. Cancer immunology research 26 30021725
2013 Cure of metastatic growth of EMT6 tumor cells in mice following manipulation of CD200:CD200R signaling. Breast cancer research and treatment 25 24166280
2017 Anti-inflammation conferred by stimulation of CD200R1 via Dok1 pathway in rat microglia after germinal matrix hemorrhage. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 24 28792282
2013 Elevated serum soluble CD200 and CD200R as surrogate markers of bone loss under bed rest conditions. Bone 24 24333170
2019 Glucocorticoids mediate stress induction of the alarmin HMGB1 and reduction of the microglia checkpoint receptor CD200R1 in limbic brain structures. Brain, behavior, and immunity 23 31078691
2017 Alterations in CD200-CD200R1 System during EAE Already Manifest at Presymptomatic Stages. Frontiers in cellular neuroscience 23 28522962
2012 CD200R1 supports HSV-1 viral replication and licenses pro-inflammatory signaling functions of TLR2. PloS one 23 23082204
2023 Cancel cancer: The immunotherapeutic potential of CD200/CD200R blockade. Frontiers in oncology 22 36756156
2023 Activation of the CD200/CD200R1 axis attenuates neuroinflammation and improves postoperative cognitive dysfunction via the PI3K/Akt/NF-κB signaling pathway in aged mice. Inflammation research : official journal of the European Histamine Research Society ... [et al.] 22 37902837
2016 Reduced expression of monocyte CD200R is associated with enhanced proinflammatory cytokine production in sarcoidosis. Scientific reports 22 27929051
2014 Aberrant CD200/CD200R1 expression and its potential role in Th17 cell differentiation, chemotaxis and osteoclastogenesis in rheumatoid arthritis. Rheumatology (Oxford, England) 22 25261692
2019 Interaction of CD200 Overexpression on Tumor Cells with CD200R1 Overexpression on Stromal Cells: An Escape from the Host Immune Response in Rectal Cancer Patients. Journal of oncology 21 30800162
2023 CD200/CD200R: Bidirectional Role in Cancer Progression and Immunotherapy. Biomedicines 20 38137547
2016 CD200R/Foxp3-mediated signalling regulates microglial activation. Scientific reports 20 27731341
2010 CD200R1 regulates the severity of arthritis but has minimal impact on the adaptive immune response. Clinical and experimental immunology 20 20735439
2024 Exploiting the CD200-CD200R immune checkpoint axis in multiple myeloma to enhance CAR T-cell therapy. Blood 18 37616575
2014 Agonistic CD200R1 DNA Aptamers Are Potent Immunosuppressants That Prolong Allogeneic Skin Graft Survival. Molecular therapy. Nucleic acids 18 25158092
2012 The expressions of CD200 and CD200R molecules on myeloid and lymphoid dendritic cells in pre-eclampsia and normal pregnancy. American journal of reproductive immunology (New York, N.Y. : 1989) 18 22462561
2012 CD200/CD200R paired potent inhibitory molecules regulating immune and inflammatory responses; Part II: CD200/CD200R potential clinical applications. Acta medica (Hradec Kralove) 18 23101267
2006 A role for the immunomodulatory molecules CD200 and CD200R in regulating bone formation. Immunology letters 18 16530849
2017 Changes in expression of the CD200 tolerance-signaling molecule and its receptor (CD200R) by villus trophoblasts during first trimester missed abortion and in chronic histiocytic intervillositis. American journal of reproductive immunology (New York, N.Y. : 1989) 17 28326648
2009 Heterogeneity in the CD200R paired receptor family. Immunogenetics 17 19967353
2017 CD200Fc Attenuates Retinal Glial Responses and RGCs Apoptosis After Optic Nerve Crush by Modulating CD200/CD200R1 Interaction. Journal of molecular neuroscience : MN 16 29280053
2023 23ME-00610, a genetically informed, first-in-class antibody targeting CD200R1 to enhance antitumor T cell function. Oncoimmunology 15 37288324
2015 The CD200 tolerance-signaling molecule and its receptor, CD200R1, are expressed in human placental villus trophoblast and in peri-implant decidua by 5 weeks' gestation. Journal of reproductive immunology 15 26123445
2021 Signaling by the inhibitory receptor CD200R is rewired by type I interferon. Science signaling 14 34637328
2018 A Synthetic Cross-Species CD200R1 Agonist Suppresses Inflammatory Immune Responses In Vivo. Molecular therapy. Nucleic acids 14 30195773
2018 The role of N-glycosylation of CD200-CD200R1 interaction in classical microglial activation. Journal of inflammation (London, England) 14 30574022
2016 Constitutively expressed Siglec-9 inhibits LPS-induced CCR7, but enhances IL-4-induced CD200R expression in human macrophages. Bioscience, biotechnology, and biochemistry 14 26923638
2012 Effect of CD200 and CD200R1 expression within tissue grafts on increased graft survival in allogeneic recipients. Immunology letters 14 23178470
2010 Potent immunosuppression by a bivalent molecule binding to CD200R and TGF-betaR. Transplantation 14 20548263
2025 CD200R1-CD200 checkpoint inhibits phagocytosis differently from SIRPα-CD47 to suppress tumor growth. Nature communications 13 40461553
2024 CD200Rhigh neutrophils with dysfunctional autophagy establish systemic immunosuppression by increasing regulatory T cells. Cellular & molecular immunology 13 38311677
2022 Altered expression of the immunoregulatory ligand-receptor pair CD200-CD200R1 in the brain of Parkinson's disease patients. NPJ Parkinson's disease 13 35296683
2016 Novel CD200 homologues iSEC1 and iSEC2 are gastrointestinal secretory cell-specific ligands of inhibitory receptor CD200R. Scientific reports 13 27819346
2024 Activation of the CD200/CD200R1 axis improves cognitive impairment by enhancing hippocampal neurogenesis via suppression of M1 microglial polarization and neuroinflammation in hypoxic-ischemic neonatal rats. International immunopharmacology 12 38237226
2023 CD200R1 promotes interleukin-17 production by group 3 innate lymphoid cells by enhancing signal transducer and activator of transcription 3 activation. Mucosal immunology 12 36623588
2023 Jingfang Granule alleviates bleomycin-induced acute lung injury via CD200-CD200R immunoregulatory pathway. Journal of ethnopharmacology 12 37011735
2021 The CD200/CD200R mechanism in mesenchymal stem cells' regulation of dendritic cells. American journal of translational research 12 34540085
2021 MicroRNA-129-5p-regulated microglial expression of the surface receptor CD200R1 controls neuroinflammation. The Journal of biological chemistry 12 34952004
2020 Parkinsonian neurotoxicants impair the anti-inflammatory response induced by IL4 in glial cells: involvement of the CD200-CD200R1 ligand-receptor pair. Scientific reports 12 32606391
2018 High Expression of CD200 and CD200R1 Distinguishes Stem and Progenitor Cell Populations within Mammary Repopulating Units. Stem cell reports 11 29937142

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