Affinage

CD200

OX-2 membrane glycoprotein · UniProt P41217

Length
278 aa
Mass
31.3 kDa
Annotated
2026-04-28
100 papers in source corpus 24 papers cited in narrative 24 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CD200 is an immunoglobulin superfamily glycoprotein that functions as a broadly expressed inhibitory ligand maintaining immune homeostasis by tonically suppressing myeloid cell activation through engagement of its receptor CD200R. Structurally composed of V-like and C-like Ig domains, CD200 binds CD200R on myeloid cells and innate lymphoid cells, triggering receptor NPLY motif phosphorylation, recruitment of the adaptor Dok2 (and Dok1 in mice) and RasGAP, which suppresses Ras/MAPK and NF-κB signaling to inhibit degranulation, cytokine production, and phagocytosis (PMID:15557172, PMID:19786546, PMID:33953190). CD200 undergoes metalloproteinase-mediated ectodomain shedding by MMP3, MMP11, and ADAM28 to release soluble CD200 that retains CD200R-binding activity and can suppress NK cell function by ERK inhibition and PPARγ-dependent induction of apoptosis (PMID:36074574, PMID:27111430). Beyond immune regulation, CD200 also activates FGFR through a motif in its first Ig-like domain to promote neuritogenesis and neuronal survival, and viral orthologues of CD200 encoded by cytomegaloviruses and rhadinoviruses engage host CD200R to evade antiviral immunity (PMID:25502296, PMID:21471432, PMID:24991004).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1984 High

    Establishing that CD200 (OX-2) is a neuronal surface antigen absent from astrocytes defined its initial cellular context and suggested a non-immune cell origin for an immunomodulatory molecule.

    Evidence Immunoperoxidase staining and double-immunofluorescence of cerebellar cultures

    PMID:6147390

    Open questions at the time
    • Receptor identity unknown
    • Function of neuronal expression unknown
    • Expression on non-neuronal tissues not yet mapped
  2. 1986 High

    Cloning of CD200 cDNA revealed its Ig superfamily membership with V-like and C-like domains, a short cytoplasmic tail, and no signaling motifs, implying it signals in trans rather than in cis.

    Evidence cDNA cloning and sequence analysis from rat

    PMID:2880589

    Open questions at the time
    • Receptor not identified
    • No functional data on immune regulation
  3. 2002 High

    Genetic ablation of CD200 revealed its essential role as an inhibitory ligand for myeloid cells: CD200-knockout mice showed spontaneous myeloid activation and increased microglial numbers with NOS2 expression, establishing the CD200–CD200R axis as a tonic immune checkpoint.

    Evidence CD200-knockout mice with immunological phenotyping and retinal immunohistochemistry

    PMID:12072366 PMID:12414514

    Open questions at the time
    • Downstream signaling mechanism of CD200R unknown
    • Identity of signaling intermediates unresolved
  4. 2004 High

    Biochemical dissection of CD200R signaling identified the Dok1/Dok2–RasGAP–SHIP pathway downstream of receptor phosphorylation, explaining how CD200 engagement suppresses Ras/MAPK cascades (ERK, JNK, p38) to inhibit mast cell degranulation and cytokine release.

    Evidence Co-immunoprecipitation, phosphorylation assays, and functional readouts in mouse bone marrow-derived mast cells

    PMID:15557172

    Open questions at the time
    • Relative contributions of Dok1 vs Dok2 in human cells unknown
    • NPLY motif requirement not yet shown
  5. 2009 High

    Quantitative binding studies and RNAi in human myeloid cells resolved that Dok2 (not Dok1) is the dominant adaptor for CD200R's NPLY motif in humans, with ~10-fold higher affinity, and that RasGAP recruitment by Dok2 is essential for inhibitory function.

    Evidence Mutant receptor expression in U937 cells, binding affinity measurements, siRNA knockdown

    PMID:19786546

    Open questions at the time
    • Structural basis of Dok2-NPLY interaction unresolved
    • Species differences in Dok1 vs Dok2 usage not fully reconciled
  6. 2007 High

    Discovery that CD200–CD200R signaling regulates macrophage-to-osteoclast fusion via NF-κB and MAPK pathways, rescued by soluble CD200, expanded the axis's role beyond classical immune suppression to bone remodeling.

    Evidence CD200-knockout mice bone phenotyping, recombinant soluble CD200 rescue, shRNA silencing, signaling pathway analysis

    PMID:17726108

    Open questions at the time
    • Mechanism by which CD200R engagement specifically licenses fusion is unclear
    • Relationship to RANK signaling not fully delineated
  7. 2014 Medium

    Identification of CD200 as a ligand for FGFR that induces receptor phosphorylation and neuritogenesis, with CD200R competing for the same binding site, revealed a dual-receptor signaling mode linking immune regulation to neurotrophic function.

    Evidence FGFR phosphorylation assays, neuritogenesis in primary neurons, competitive binding experiments

    PMID:25502296

    Open questions at the time
    • FGFR interaction not independently confirmed by a second laboratory
    • Structural details of CD200–FGFR interface unknown
    • In vivo relevance of FGFR activation by CD200 not demonstrated
  8. 2016 High

    Characterization of CD200 ectodomain shedding by ADAM28 (and later MMP3/MMP11) established that soluble CD200 is a biologically active fragment retaining CD200R-binding and signaling capacity, broadening its functional reach beyond cell-cell contact.

    Evidence Western blot with domain-specific antibodies, ADAM28 silencing, CD200R phosphorylation assays; MMP inhibitor studies in BCC

    PMID:27111430 PMID:36074574

    Open questions at the time
    • Relative contributions of individual sheddases in different tissues unknown
    • Regulation of shedding events not defined
  9. 2019 High

    Demonstration that Leishmania amazonensis exploits endosomal TLR9/MyD88/TRIF signaling to upregulate CD200, which then suppresses iNOS/NO to promote parasite survival, established CD200 as a pathogen-hijacked immune checkpoint.

    Evidence TLR9/MyD88/TRIF genetic knockouts, microvesicle isolation, in vivo infection model

    PMID:31092731

    Open questions at the time
    • Whether other pathogens use similar TLR9-CD200 pathway unknown
    • Mechanism of CD200 transcriptional induction downstream of TLR9 not fully elucidated
  10. 2021 Medium

    Multiple studies expanded CD200R-expressing target cell types to include ILC2s (where CD200R inhibits NF-κB signaling and type 2 cytokine production) and T cells (where tumor CD200 suppresses OXPHOS metabolism), establishing CD200 as a broad immune checkpoint beyond myeloid cells.

    Evidence CD200R engagement assays on ILC2s with NF-κB analysis; isogenic CD200+/− tumor lines with CyTOF and metabolic profiling in humanized mice

    PMID:33953190 PMID:34326171

    Open questions at the time
    • Direct signaling intermediates in ILC2s downstream of CD200R not fully mapped
    • Mechanism of T cell OXPHOS suppression by CD200R is unclear
  11. 2022 High

    Full delineation of soluble CD200-mediated NK cell suppression in basal cell carcinoma identified a MMP3/MMP11-shedding → CD200R → ERK inhibition → PPARγ activation → Fas/FADD-dependent apoptosis pathway, providing a complete mechanistic chain from tumor immune evasion to NK cell death.

    Evidence MMP inhibitor studies, CD200R blocking, MAPK/PPARγ pathway analysis, Fas/FADD expression, NK killing assays in BCC

    PMID:36074574

    Open questions at the time
    • Whether this PPARγ-Fas apoptosis pathway operates in other immune cell types unknown
    • Therapeutic window for shedding or CD200R blockade not assessed

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of CD200–CD200R and CD200–FGFR interactions, the precise transcriptional regulation of CD200 across tissues, and whether therapeutic disruption of CD200 shedding can selectively restore anti-tumor immunity without breaking peripheral tolerance.
  • No crystal structure of CD200–CD200R complex
  • Transcriptional regulation beyond p53 and TLR9 pathways poorly characterized
  • Therapeutic index of CD200 axis blockade not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 5 GO:0098772 molecular function regulator activity 4
Localization
GO:0005886 plasma membrane 4 GO:0005576 extracellular region 2
Pathway
R-HSA-168256 Immune System 7 R-HSA-162582 Signal Transduction 5 R-HSA-5357801 Programmed Cell Death 2
Partners
ADAM28CD200R1DOK1DOK2FGFR1MMP11MMP3RASA1

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1986 CD200 (MRC OX-2) is a member of the immunoglobulin superfamily with a structure resembling an Ig light chain, containing a V-like domain and a C-like domain followed by transmembrane and cytoplasmic sections, encoded by 248 amino acids. cDNA cloning and sequence analysis Biochemical Society symposium High 2880589
1984 CD200 (OX-2 antigen) is localized on the surfaces of neurons (all tetanus toxin-positive cells in cerebellar interneurone cultures) but not on GFAP-positive astrocytes, establishing its neuronal membrane localization. Indirect immunoperoxidase staining and double-immunofluorescence of cerebellar cultures with OX-2 antibody and tetanus toxin Journal of neurochemistry High 6147390
2002 CD200 functions as a ligand for a myeloid-restricted receptor (CD200R) and delivers inhibitory signals to myeloid cells; CD200-deficient mice show increased myeloid cell activation upon immunological stimulation. CD200 knockout mouse model with functional immunological readouts Trends in immunology High 12072366
2004 Upon CD200 binding, CD200R is phosphorylated on tyrosine and recruits adaptor proteins Dok1 and Dok2; Dok1 then binds SHIP and both Dok1 and Dok2 recruit RasGAP, which inhibits Ras/MAPK pathways (ERK, JNK, p38), resulting in inhibition of mast cell degranulation and cytokine production. Biochemical phosphorylation assays, co-immunoprecipitation of Dok1/Dok2/SHIP/RasGAP, functional assays in mouse bone marrow-derived mast cells Journal of immunology High 15557172
2009 In human myeloid cells, CD200R inhibition is mediated via its NPLY motif; Dok2 binds directly to the phosphorylated NPLY motif with ~10-fold higher affinity than Dok1 (Kd ~1 µM at 37°C), is phosphorylated upon CD200R engagement, and recruits RasGAP. Knockdown of Dok2 and RasGAP (but not Dok1 or SHIP) abolishes CD200R-mediated inhibition. Mutant receptor expression in U937 cells, direct binding affinity measurements, RNA interference knockdown, functional inhibition assays Journal of immunology High 19786546
2002 CD200 expressed constitutively on retinal neurons and vascular endothelium regulates retinal microglial activation; CD200-deficient mice show increased microglial numbers and inducible NOS2 expression in microglia at baseline, demonstrating that CD200:CD200R axis controls tonic microglial suppression. CD200 knockout mouse model, immunohistochemistry for NOS2, microglial counting The American journal of pathology High 12414514
2003 CD200 is a p53-target gene; its expression increases on dendritic cells undergoing apoptosis through both p53-dependent and caspase-dependent pathways, and CD200 expression on apoptotic DCs suppresses proinflammatory cytokine responses to self-antigens and is required for UVB-mediated tolerance. p53 pathway analysis, caspase inhibitor experiments, in vitro cytokine assays, in vivo UVB tolerance model Blood Medium 14644999
2007 CD200 engagement of CD200R at the initiation of macrophage fusion regulates further differentiation to osteoclasts; CD200-deficient mice have fewer osteoclasts and more bone, and a soluble CD200 extracellular domain rescues fusion and RANK-downstream NF-κB and MAP kinase signaling in CD200-/- macrophages. CD200 knockout mouse model, recombinant soluble CD200/CD200R proteins, shRNA silencing of CD200R, NF-κB and MAPK pathway analysis Proceedings of the National Academy of Sciences of the United States of America High 17726108
2004 CD200 receptor-like 3 (a CD200R family member) associates with the activating adaptor DAP12 at the cell surface; the second Ig-like domain (exon 4) is required for cell surface expression and DAP12 recruitment, and splice variants generate unique cytoplasmic domains contributing to DAP12 pairing. Microarray screen, splice variant characterization, functional surface expression assays in basophils and mast cells The Journal of biological chemistry Medium 15471863
2009 Endothelial CD200 mediates T-cell adhesion to endothelium through physical CD200-CD200R binding; a synthetic CD200 agonist peptide can trigger CD200R signaling in macrophages to suppress their adhesion to endothelium. Endothelial CD200 expression is differentially regulated by LPS in different vascular beds. Functional adhesion assays, antibody blocking, synthetic peptide agonist treatment, in vivo and in vitro LPS stimulation Journal of anatomy Medium 19166481
2011 Rat cytomegalovirus encodes a CD200 orthologue (e127) that is expressed at the cell surface on infected cells and binds the host CD200R with the same affinity as the host CD200 protein, acting as a viral mimic to potentially downregulate immune responses. Cell surface expression assays, binding affinity measurements of e127 vs. host CD200 for CD200R Journal of virology Medium 21471432
2014 CD200 can interact with and activate the fibroblast growth factor receptor (FGFR), inducing neuritogenesis and promoting neuronal survival; CD200R abrogates CD200-induced FGFR phosphorylation, and a minimal FGFR-binding motif was identified in the first Ig-like module of CD200 that overlaps with the CD200R binding site. FGFR phosphorylation assays, neuritogenesis assays in primary neurons, competitive binding with CD200R, motif identification Molecular neurobiology Medium 25502296
2016 CD200 expression is regulated by PPAR-γ in glial cells; the PPAR-γ agonist 15d-PGJ2 prevents CD200 upregulation and CD200R1 downregulation in reactive glia, and CD200-CD200R1 interaction mediates the anti-inflammatory and neuroprotective effects of PPAR-γ agonists in neuron-microglia cocultures. Primary neuronal and glial cultures, LPS/IFN-γ activation, PPAR-γ agonist treatment, neurotoxicity assays Glia Medium 24639050
2016 CD200 deficiency in microglia leads to increased phagocytic activity associated with increased lysosomal activity and decreased mTOR signaling; inhibiting mTOR with rapamycin increases phagocytosis similarly, indicating that CD200-CD200R signaling regulates lysosomal/mTOR-dependent phagocytosis in microglia. CD200-deficient mouse microglia isolation, phagocytosis assays, lysosomal activity measurement, mTOR inhibition with rapamycin Molecular neurobiology Medium 27830533
2016 CD200-Fc (soluble CD200 fusion protein) downregulates toll-like receptor 4 (TLR4) expression in macrophages, thereby inhibiting macrophage phagocytosis of oligodendrocyte precursor cells; in vivo treatment with CD200-Fc suppressed TLR4 expression in circulating macrophages and improved myelination after white matter ischemia. Primary cell culture phagocytosis assays, TLR4 blocking, CD200-Fc treatment in endothelin-1 white matter ischemia model Journal of cerebral blood flow and metabolism Medium 26661156
2019 Leishmania amazonensis induces CD200 expression in macrophages through phagocytosis-mediated activation of endosomal TLR9/MyD88/TRIF signaling; Leishmania microvesicles containing DNA fragments activate TLR9-dependent CD200 expression, which then inhibits iNOS/NO signaling to promote intracellular parasite survival. Genetic knockouts/knockdowns of TLR9/MyD88/TRIF, microvesicle isolation, iNOS/NO pathway analysis, in vivo infection model JCI insight High 31092731
2022 In basal cell carcinoma, CD200 undergoes ectodomain shedding by metalloproteinases MMP3 and MMP11, releasing biologically active soluble CD200 into the tumor microenvironment; soluble CD200 binds CD200R on NK cells to suppress MAPK signaling, blocking IFN-γ release and direct killing, and reduced ERK phosphorylation activates PPARγ-regulated gene transcription leading to Fas/FADD membrane accumulation and activation-induced NK cell apoptosis. MMP inhibitor studies, CD200R blocking, MAPK/ERK pathway analysis, PPARγ pathway analysis, Fas/FADD expression assays, NK cell killing assays The Journal of clinical investigation High 36074574
2016 CD200 undergoes ectodomain shedding (partially mediated by ADAM28) to generate soluble CD200 that retains the functional extracellular domain but lacks the cytoplasmic domain; shed CD200 can bind to and phosphorylate CD200R1 on receptor-expressing cells. Western blot with extracellular vs. cytoplasmic domain antibodies, ADAM28 silencing, flow cytometry of surface CD200 loss, functional CD200R1 phosphorylation assay PloS one Medium 27111430
2021 CD200R on ILC2s is inducible, and CD200R engagement inhibits ILC2 activation, proliferation, and type 2 cytokine production by inhibiting both canonical and non-canonical NF-κB signaling pathways. Flow cytometry of CD200R expression on murine and human ILC2s, CD200R engagement functional assays, NF-κB pathway analysis, in vivo asthma models Nature communications Medium 33953190
2021 CD200 expression on AML cells suppresses OXPHOS metabolic activity in T cells, impairing their effector function; this represents a stem cell-specific immune evasion mechanism. Isogenic CD200+ vs CD200- cell line models, CyTOF, RNA-sequencing, PBMC-humanized mouse models, metabolic assays Journal for immunotherapy of cancer Medium 34326171
2021 CD200-CD200R1 signaling from pro-resolving CD200+DKK3+ fibroblasts stabilizes type 2 innate lymphoid cell phenotype and induces resolution of arthritis. Single-cell RNA-sequencing, spatial transcriptomics, CD200-CD200R1 signaling blocking experiments, in vivo arthritis model Nature immunology Medium 38396288
2023 CD200-CD200R signaling between amacrine cells and microglia is dysregulated in early diabetic retinopathy; targeting CD200R attenuates high glucose-induced microglial inflammation and phagocytosis in vitro, and CD200R targeting in vivo prevents visual dysfunction and retinal inflammation in diabetic mice. Microglia ablation, flow cytometry, transcriptomics, CD200R pharmacological targeting in vitro and in vivo diabetic mouse model Proceedings of the National Academy of Sciences of the United States of America Medium 37903272
2021 CD200 expression on cSCC tumors induces cathepsin K (Ctsk) expression in CD11B+CD200R+ infiltrating myeloid cells via engagement of the CD200-CD200R axis; Ctsk inhibition (but not MMP inhibition) blocks cSCC cell migration, and CD200 disruption plus Ctsk inhibition reduces metastasis in vivo. RNA sequencing of tumor-infiltrating myeloid cells, coculture system establishing CD200-CD200R-dependent Ctsk induction, pharmacological Ctsk inhibition, in vivo metastasis model with CD200 knockout Cancer research Medium 34183355
2014 RRV vCD200 (viral CD200 orthologue) limits immune responses against RRV at early times post-infection and impacts viral loads in vivo, demonstrating that viral CD200 mimic functionally engages host CD200R to suppress antiviral immunity. vCD200-deletion mutant RRV in vivo infection of rhesus macaques, viral load measurements, immune response quantification Journal of virology Medium 24991004

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 Cell transformation by the superoxide-generating oxidase Mox1. Nature 1215 10485709
2002 CD200 and membrane protein interactions in the control of myeloid cells. Trends in immunology 335 12072366
2004 Molecular mechanisms of CD200 inhibition of mast cell activation. Journal of immunology (Baltimore, Md. : 1950) 200 15557172
2006 Regulation of myeloid cell function through the CD200 receptor. Journal of immunology (Baltimore, Md. : 1950) 189 16365410
2002 Constitutive retinal CD200 expression regulates resident microglia and activation state of inflammatory cells during experimental autoimmune uveoretinitis. The American journal of pathology 175 12414514
1998 Proteasome-dependent degradation of oxidized proteins in MRC-5 fibroblasts. FEBS letters 151 9872410
2000 Protein oxidation and degradation during proliferative senescence of human MRC-5 fibroblasts. Free radical biology & medicine 126 10754265
2009 Essential roles for Dok2 and RasGAP in CD200 receptor-mediated regulation of human myeloid cells. Journal of immunology (Baltimore, Md. : 1950) 123 19786546
2007 Elevated neuronal expression of CD200 protects Wlds mice from inflammation-mediated neurodegeneration. The American journal of pathology 123 17456775
2007 Monoclonal antibody-mediated CD200 receptor signaling suppresses macrophage activation and tissue damage in experimental autoimmune uveoretinitis. The American journal of pathology 110 17600119
2009 Expression of the inhibitory CD200 receptor is associated with alternative macrophage activation. Journal of innate immunity 101 20375636
1984 Localisation of the MRC OX-2 glycoprotein on the surfaces of neurones. Journal of neurochemistry 99 6147390
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 90 33562512
2008 Immune modulation by melanoma and ovarian tumor cells through expression of the immunosuppressive molecule CD200. Cancer immunology, immunotherapy : CII 84 18060403
2008 CNS inflammation and neuronal degeneration is aggravated by impaired CD200-CD200R-mediated macrophage silencing. Journal of neuroimmunology 75 18164423
2015 Silica Nanoparticles Induce Oxidative Stress and Autophagy but Not Apoptosis in the MRC-5 Cell Line. International journal of molecular sciences 74 26690408
2014 The CD200-CD200R1 inhibitory signaling pathway: immune regulation and host-pathogen interactions. Advances in immunology 73 24388216
1998 Increased expression of the novel molecule OX-2 is involved in prolongation of murine renal allograft survival. Transplantation 70 9583873
2004 Robotic nanolitre protein crystallisation at the MRC Laboratory of Molecular Biology. Progress in biophysics and molecular biology 69 15652247
2003 CD200 is a novel p53-target gene involved in apoptosis-associated immune tolerance. Blood 64 14644999
1986 Neuronal/lymphoid membrane glycoprotein MRC OX-2 is a member of the immunoglobulin superfamily with a light-chain-like structure. Biochemical Society symposium 64 2880589
2012 Characterization and functionality of the CD200-CD200R system during mesenchymal stromal cell interactions with T-lymphocytes. Immunology letters 63 22575528
2011 CD200-CD200R signaling suppresses anti-tumor responses independently of CD200 expression on the tumor. Oncogene 63 22020332
2014 CD200 in CNS tumor-induced immunosuppression: the role for CD200 pathway blockade in targeted immunotherapy. Journal for immunotherapy of cancer 62 25598973
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
2015 The anti-inflammatory glycoprotein, CD200, restores neurogenesis and enhances amyloid phagocytosis in a mouse model of Alzheimer's disease. Neurobiology of aging 59 26315370
2020 CD200-CD200R Pathway in the Regulation of Tumor Immune Microenvironment and Immunotherapy. Advances in experimental medicine and biology 56 32030689
2012 CD200 positive human mesenchymal stem cells suppress TNF-alpha secretion from CD200 receptor positive macrophage-like cells. PloS one 54 22363701
2009 Breast cancer cell CD200 expression regulates immune response to EMT6 tumor cells in mice. Breast cancer research and treatment 52 19953316
2004 CD200 receptor family members represent novel DAP12-associated activating receptors on basophils and mast cells. The Journal of biological chemistry 51 15471863
2010 The role of CD200 in immunity to B cell lymphoma. Journal of leukocyte biology 48 20442224
2014 CD200R1 and CD200 expression are regulated by PPAR-γ in activated glial cells. Glia 47 24639050
1994 Isolation of a diverged homeobox gene, MOX1, from the BRCA1 region on 17q21 by solution hybrid capture. Human molecular genetics 47 7987315
2024 CD200+ fibroblasts form a pro-resolving mesenchymal network in arthritis. Nature immunology 46 38396288
2003 Placental trophoblast from successful human pregnancies expresses the tolerance signaling molecule, CD200 (OX-2). American journal of reproductive immunology (New York, N.Y. : 1989) 46 14629022
2009 Endothelial CD200 is heterogeneously distributed, regulated and involved in immune cell-endothelium interactions. Journal of anatomy 45 19166481
2021 CD200-CD200R immune checkpoint engagement regulates ILC2 effector function and ameliorates lung inflammation in asthma. Nature communications 41 33953190
2019 CD200-CD200R1 inhibitory signaling prevents spontaneous bacterial infection and promotes resolution of neuroinflammation and recovery after stroke. Journal of neuroinflammation 41 30777093
2015 CD200 restrains macrophage attack on oligodendrocyte precursors via toll-like receptor 4 downregulation. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 41 26661156
2001 Transplant tolerance modifying antibody to CD200 receptor, but not CD200, alters cytokine production profile from stimulated macrophages. European journal of immunology 41 11477545
2015 Upregulation of CD200 is associated with regulatory T cell expansion and disease progression in multiple myeloma. Hematological oncology 40 26033514
1996 Differential localization of Mox-1 and Mox-2 proteins indicates distinct roles during development. The International journal of developmental biology 40 9032023
2009 Expression of a CD200 transgene is necessary for induction but not maintenance of tolerance to cardiac and skin allografts. Journal of immunology (Baltimore, Md. : 1950) 39 19592654
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
2018 CD200-, CX3CL1-, and TREM2-mediated neuron-microglia interactions and their involvements in Alzheimer's disease. Reviews in the neurosciences 38 29729150
2016 Downregulation of CD47 and CD200 in patients with focal cortical dysplasia type IIb and tuberous sclerosis complex. Journal of neuroinflammation 38 27095555
2016 Analysis of the Impact of CD200 on Phagocytosis. Molecular neurobiology 38 27830533
2017 Reduced CD200 expression is associated with altered Th1/Th2 cytokine production in placental trophoblasts from preeclampsia. American journal of reproductive immunology (New York, N.Y. : 1989) 37 28940677
2022 CD200 ectodomain shedding into the tumor microenvironment leads to NK cell dysfunction and apoptosis. The Journal of clinical investigation 36 36074574
2002 Binding and invasion of HeLa and MRC-5 cells by Streptococcus agalactiae. Microbiology (Reading, England) 36 12480896
2018 CD200 modulates spinal cord injury neuroinflammation and outcome through CD200R1. Brain, behavior, and immunity 35 29870752
2011 Orexins/hypocretins acting at Gi protein-coupled OX 2 receptors inhibit cyclic AMP synthesis in the primary neuronal cultures. Journal of molecular neuroscience : MN 34 21547533
2001 Homeodomain proteins Mox1 and Mox2 associate with Pax1 and Pax3 transcription factors. FEBS letters 34 11423130
2000 The homeobox genes MSX2 and MOX2 are candidates for regulating epithelial-mesenchymal cell interactions in the human placenta. Placenta 34 10831122
2013 CD200-expressing human basal cell carcinoma cells initiate tumor growth. Proceedings of the National Academy of Sciences of the United States of America 32 23292936
2019 CD200 dysfunction in neuron contributes to synaptic deficits and cognitive impairment. Biochemical and biophysical research communications 31 31277944
2021 Overexpression of CD200 is a Stem Cell-Specific Mechanism of Immune Evasion in AML. Journal for immunotherapy of cancer 30 34326171
2019 TLR9/MyD88/TRIF signaling activates host immune inhibitory CD200 in Leishmania infection. JCI insight 30 31092731
2013 CD200 upregulation in vascular endothelium surrounding cutaneous squamous cell carcinoma. JAMA dermatology 30 23560298
2008 CD200-dependent and nonCD200-dependent pathways of NK cell suppression by human IVIG. Journal of assisted reproduction and genetics 29 18256920
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
2019 Circular RNA ANKRD36 attends to lipopolysaccharide-aroused MRC-5 cell injury via regulating microRNA-31-3p. BioFactors (Oxford, England) 28 31793082
2017 CD200 Expression in Neuroendocrine Neoplasms. American journal of clinical pathology 28 28821198
2017 CD11b and CD200 on Circulating Monocytes Differentiate Two Angiographic Subtypes of Polypoidal Choroidal Vasculopathy. Investigative ophthalmology & visual science 27 29049725
2021 The CD200-CD200R Axis Promotes Squamous Cell Carcinoma Metastasis via Regulation of Cathepsin K. Cancer research 26 34183355
2020 CD200 and Chronic Lymphocytic Leukemia: Biological and Clinical Relevance. Frontiers in oncology 26 33324560
2019 CD200-CD200R signaling and diseases: a potential therapeutic target? International journal of physiology, pathophysiology and pharmacology 25 31993106
2017 Orexin OX2 Receptor Antagonists as Sleep Aids. Current topics in behavioral neurosciences 25 27909987
2013 Elevated serum soluble CD200 and CD200R as surrogate markers of bone loss under bed rest conditions. Bone 24 24333170
2018 Loss of neuronal CD200 contributed to microglial activation after acute cerebral ischemia in mice. Neuroscience letters 23 29729356
2016 ROS-dependent HMGA2 upregulation mediates Cd-induced proliferation in MRC-5 cells. Toxicology in vitro : an international journal published in association with BIBRA 23 27071802
2012 CD200 expression in B-cell chronic lymphoproliferative disorders. Journal of investigative medicine : the official publication of the American Federation for Clinical Research 23 22064604
2021 Immunomodulatory effects of phytosomal curcumin on related-micro RNAs, CD200 expression and inflammatory pathways in dental pulp stem cells. Cell biochemistry and function 22 34235754
2017 Alterations in CD200-CD200R1 System during EAE Already Manifest at Presymptomatic Stages. Frontiers in cellular neuroscience 22 28522962
2016 Characterization of CD200 Ectodomain Shedding. PloS one 22 27111430
2011 Cytomegalovirus e127 protein interacts with the inhibitory CD200 receptor. Journal of virology 22 21471232
1978 Comparison of WI-38, MRC-5, and IMR-90 cell strains for isolation of viruses from clinical specimens. Journal of clinical microbiology 22 211143
2023 Cancel cancer: The immunotherapeutic potential of CD200/CD200R blockade. Frontiers in oncology 21 36756156
2020 Estrogen-regulated CD200 inhibits macrophage phagocytosis in endometriosis. Journal of reproductive immunology 21 32014721
2020 CD200 is overexpressed in neuroblastoma and regulates tumor immune microenvironment. Cancer immunology, immunotherapy : CII 21 32514618
2016 Over-Expression of CD200 Protects Mice from Dextran Sodium Sulfate Induced Colitis. PloS one 21 26841120
2014 Immunomodulator CD200 Promotes Neurotrophic Activity by Interacting with and Activating the Fibroblast Growth Factor Receptor. Molecular neurobiology 21 25502296
2013 Dissection of agonistic and blocking effects of CD200 receptor antibodies. PloS one 21 23691022
2023 The immunoregulatory protein CD200 as a potentially lucrative yet elusive target for cancer therapy. Oncotarget 19 36738455
2023 CD200/CD200R: Bidirectional Role in Cancer Progression and Immunotherapy. Biomedicines 19 38137547
2016 Low expression of CD200 predicts shorter time-to-treatment in chronic lymphocytic leukemia. Oncotarget 19 26910908
2015 Lung CD200 Receptor Activation Abrogates Airway Hyperresponsiveness in Experimental Asthma. American journal of respiratory cell and molecular biology 19 25569356
2024 Exploiting the CD200-CD200R immune checkpoint axis in multiple myeloma to enhance CAR T-cell therapy. Blood 18 37616575
2017 Checkpoint blockade in solid tumors and B-cell malignancies, with special consideration of the role of CD200. Cancer management and research 18 29180896
2016 Tumor-derived vaccines containing CD200 inhibit immune activation: implications for immunotherapy. Immunotherapy 18 27485078
2014 The rhesus rhadinovirus CD200 homologue affects immune responses and viral loads during in vivo infection. Journal of virology 18 24991004
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
1995 Isolation of the human MOX2 homeobox gene and localization to chromosome 7p22.1-p21.3. Genomics 18 7607679
2022 Knockdown of FBLN2 suppresses TGF-β1-induced MRC-5 cell migration and fibrosis by downregulating VTN. Tissue & cell 17 36608640
2018 Forced expression of CD200 improves the differentiation capability and immunoregulatory functions of mesenchymal stromal cells. Biotechnology letters 17 29740779
2017 Th1/Th2 PB balance and CD200 expression of patients with active severe alopecia areata. Experimental and therapeutic medicine 17 28587354
2015 Adhesion of MRC-5 and A549 cells on poly(dimethylsiloxane) surface modified by proteins. Electrophoresis 17 26311334
2023 GAS6 From CD200+ Adipose-Derived Stem Cells Mitigates Colonic Inflammation in a Macrophage-Dependent Manner. Journal of Crohn's & colitis 16 36006655
2020 CD200 maintains the region-specific phenotype of microglia in the midbrain and its role in Parkinson's disease. Glia 15 32112601