Affinage

CD47

Leukocyte surface antigen CD47 · UniProt Q08722

Length
323 aa
Mass
35.2 kDa
Annotated
2026-06-13
100 papers in source corpus 23 papers cited in narrative 23 extracted findings
Cross-family judge vs UniProt: Affinage preferred

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CD47 is a ubiquitously expressed transmembrane receptor that functions as a self-recognition signal restraining phagocytic and immune clearance of cells (PMID:10856220, PMID:11306274). Its canonical activity is to bind the inhibitory receptor SIRPα on splenic and myeloid phagocytes, marking red blood cells and other targets as 'self' and preventing their engulfment (PMID:10856220); this engagement is species- and cell-type specific and operates in a threshold-dependent manner that can be overridden by target rigidity-driven myosin-II activation at the phagocytic synapse (PMID:16291597, PMID:25411427). Downstream of CD47-liganded SIRPα, the protein tyrosine phosphatases SHP-1 and SHP-2 are recruited (PMID:19144521), and productive inhibitory signaling requires SENP8-mediated deneddylation of SHP2 at K358/K364 to relieve its autoinhibited conformation and permit substrate dephosphorylation at the phagocytic cup (PMID:36626230). This 'don't eat me' axis governs efferocytosis in diverse settings: it limits clearance of apoptotic and senescent cells in atherosclerosis (PMID:27437576, PMID:36459066, PMID:34940829), restrains developmental microglial synaptic pruning (PMID:30308165), and counteracts NK-cell cytotoxicity through SIRPα on activated NK cells (PMID:33416832). CD47 is also a high-affinity receptor for thrombospondin-1, through which it organizes a supramolecular complex with integrins, heterotrimeric Gi proteins, and cholesterol to modulate integrin function (PMID:11306274), suppresses AKT-eNOS-dependent lymphangiogenesis (PMID:37259865), inhibits Th17 and promotes Treg differentiation (PMID:31214201), and regulates autophagic flux to control radiosensitivity (PMID:22874555); it further associates with Fas to augment apoptotic signaling (PMID:15917238) and with TLR2 to drive TSP-1-dependent suppression of innate antibacterial activity (PMID:39536084). CD47 abundance is transcriptionally driven by MYC, IFN-γ via JAK1/STAT1/IRF1, and NFκB1 p50 (PMID:26966191, PMID:34171557, PMID:35990913), and stabilized post-translationally by EGFR-c-Src-mediated Y288 phosphorylation that blocks TRIM21-dependent K99/102 polyubiquitylation and proteasomal degradation (PMID:37541303). Therapeutically, CD47 blockade requires dendritic-cell cross-priming and STING-dependent cytosolic DNA sensing rather than macrophage phagocytosis alone for antitumor T-cell responses (PMID:26322579), and CD47 expression is essential for the persistence of adoptively transferred CAR T cells in vivo (PMID:38750365).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 2000 High

    Established CD47's foundational role as a self-marker: it was unknown how cells avoid phagocytic clearance, and CD47-null RBCs demonstrated that CD47-SIRPα engagement is required to prevent splenic macrophage destruction.

    Evidence In vivo adoptive transfer of CD47-null vs. wild-type mouse RBCs with macrophage phagocytosis assays

    PMID:10856220

    Open questions at the time
    • Did not resolve the intracellular signaling steps downstream of SIRPα
    • Limited to RBC clearance in spleen
  2. 2001 Medium

    Defined CD47 as a multifunctional receptor beyond self-recognition by identifying thrombospondin as a ligand and placing CD47 in a complex with integrins, Gi proteins, and cholesterol that modulates integrin function.

    Evidence Biochemical reconstitution, peptide agonist assays, and co-immunoprecipitation of complex components

    PMID:11306274

    Open questions at the time
    • Abstract-level summary of prior biochemistry, not a single primary dataset
    • Stoichiometry and architecture of the supramolecular complex undefined
  3. 2005 High

    Connected CD47 to apoptotic signaling, showing it physically associates with Fas and is required for efficient Fas-mediated death, expanding CD47 function from anti-phagocytic to pro-apoptotic.

    Evidence CD47-knockout Jurkat cells with re-expression rescue, reciprocal Fas/CD47 Co-IP, and primary T cells from CD47-null mice

    PMID:15917238

    Open questions at the time
    • Molecular mechanism by which CD47 couples to caspase activation unresolved
    • Relationship to SIRPα signaling not addressed
  4. 2005 Medium

    Quantified the CD47-SIRPα interaction's species and cell-type specificity, explaining why phagocytes do not adhere to RBCs under physiological conditions despite CD47 display.

    Evidence SIRPα1 binding assays, atomic force microscopy, centrifugation-based adhesion, and antibody inhibition

    PMID:16291597

    Open questions at the time
    • Single lab biophysical characterization
    • Functional consequence of weak MSC binding not pursued
  5. 2009 Medium

    Identified the inhibitory effectors of the axis, establishing that SIRPα recruits SHP-1 and SHP-2 and that CD47-SIRPα is a bidirectional system regulating migration and phagocytosis.

    Evidence Biochemical binding assays, structural analysis, and functional phagocytosis assays (review synthesis)

    PMID:19144521

    Open questions at the time
    • Did not define the regulatory steps controlling SHP-2 activation
    • SIRPβ non-binding mechanism unexplained
  6. 2012 High

    Revealed a thrombospondin/CD47-linked cytoprotection pathway, showing CD47 loss or blockade activates autophagic flux that mediates radioprotection of T and endothelial cells.

    Evidence CD47-null cells with re-expression, siRNA/pharmacological autophagy inhibition, EM, flow cytometry, and Western blot

    PMID:22874555

    Open questions at the time
    • Signaling link between CD47 and autophagy machinery not defined
    • Whether SIRPα or TSP1 mediates the effect unclear
  7. 2015 High

    Placed CD47 under direct oncogenic transcriptional control, showing MYC binds the Cd47 promoter and that CD47 contributes to MYC-driven immune evasion.

    Evidence ChIP of MYC at Cd47/Pd-l1 promoters, inducible MYC mouse tumors, and CD47 enforced-expression rescue

    PMID:26966191

    Open questions at the time
    • Did not address other transcriptional inputs
    • Relative contribution of CD47 vs. PD-L1 to evasion not dissected
  8. 2015 High

    Redefined the cellular basis of CD47-blockade therapy, demonstrating it requires dendritic-cell cross-priming and STING-dependent DNA sensing rather than macrophage phagocytosis alone.

    Evidence Syngeneic tumor models with T cell-deficient mice, STING/MyD88/TRIF knockouts, and macrophage/DC depletion

    PMID:26322579

    Open questions at the time
    • Source of cytosolic DNA activating STING not identified
    • How CD47 blockade triggers DC priming mechanistically unresolved
  9. 2016 High

    Extended the anti-efferocytosis role to cardiovascular disease, identifying TNF-α-driven CD47 upregulation as a barrier to apoptotic cell clearance in atherosclerosis reversible by CD47 blockade.

    Evidence Multiple atherosclerosis mouse models, anti-CD47 antibody treatment, and efferocytosis assays

    PMID:27437576

    Open questions at the time
    • Transcription factor downstream of TNF-α not defined here
    • Cell-type-specific contributions not separated
  10. 2018 High

    Demonstrated a neurodevelopmental function, showing CD47-SIRPα protects active synapses from excessive microglial pruning in an activity-dependent manner.

    Evidence CD47 knockout mice, microglial engulfment assays, electrophysiology, and confocal imaging of the retinogeniculate system

    PMID:30308165

    Open questions at the time
    • How neuronal activity regulates synaptic CD47 levels unknown
    • Microglial SHP signaling in pruning not directly tested
  11. 2021 Medium

    Established transcriptional and innate-immune extensions of CD47 regulation: IFN-γ induces CD47 via JAK1/STAT1/IRF1 to strengthen SIRPα binding, and NK cells use IL-2-induced SIRPα to read target CD47.

    Evidence siRNA and JAK inhibitor studies with phagocytosis assays (IFN-γ); NK SIRPα characterization with CD47-overexpressing targets and cytotoxicity assays

    PMID:33416832 PMID:34171557

    Open questions at the time
    • Single-lab pathway epistasis for the IFN-γ axis
    • NK SIRPα threshold-setting mechanism not defined
  12. 2022 High

    Resolved cell-specific and context-specific roles in atherosclerosis and senescence: myeloid CD47 and SIRPα have opposite effects, statins suppress CD47 via NFκB1 p50, and senescent cells exploit QPCT/L-modified CD47 to block efferocytosis.

    Evidence Cell-specific and global conditional knockout mice, statin treatment with NFκB1 p50 translocation assays, senescent cell models with QPCT/L inhibition, and efferocytosis assays

    PMID:34940829 PMID:35990913 PMID:36459066

    Open questions at the time
    • Mechanism distinguishing CD47 vs. SIRPα myeloid outcomes incomplete
    • QPCT/L modification site on CD47 not fully mapped in these studies
  13. 2022 Medium

    Showed CD47 can act in trans via exosomal transfer, with cross-dressed CD47 inhibiting phagocytosis through SIRPα but failing to transmit the pro-death signal of autogenous CD47.

    Evidence Exosome isolation, surface CD47 flow cytometry, SIRPα binding, and comparative phagocytosis and cell-death assays

    PMID:36454036

    Open questions at the time
    • Structural basis for the death-signaling difference unknown
    • Physiological prevalence of cross-dressing untested
  14. 2023 High

    Defined post-translational stabilization of CD47, showing EGFR-c-Src Y288 phosphorylation blocks TRIM21-mediated K99/102 polyubiquitylation and degradation, controlling surface CD47 and phagocytosis.

    Evidence Co-IP, Y288F and K99/102R knock-in mutagenesis, in vitro kinase and ubiquitylation assays, phagocytosis assays, and in vivo brain tumor models

    PMID:37541303

    Open questions at the time
    • Upstream signals coupling EGFR activity to CD47 in vivo not fully mapped
    • Whether TRIM21 acts on other CD47 pools unknown
  15. 2023 High

    Uncovered a NEDD8 regulatory layer in inhibitory signaling, showing SHP2 is constitutively neddylated and that CD47-SIRPα-triggered SENP8 deneddylation is required to activate SHP2 at the phagocytic cup.

    Evidence Mass spectrometry mapping of neddylation sites, K358/K364 mutagenesis, SENP8 siRNA/KO, and substrate dephosphorylation and phagocytosis assays

    PMID:36626230

    Open questions at the time
    • How SIRPα engagement activates SENP8 not defined
    • Role of SHP-1 neddylation not addressed
  16. 2023 High

    Linked TSP1-CD47 signaling to lymphatic biology, showing CD47 mediates TSP1 inhibition of VEGF-C-driven AKT-eNOS signaling and lymphangiogenesis with consequences for atherosclerosis.

    Evidence LEC-specific Cd47 knockout mice, AAV8-PCSK9 atherosclerosis model, siRNA, AKT/eNOS Western blots, and Matrigel plug assays

    PMID:37259865

    Open questions at the time
    • Direct biochemical link between CD47 and AKT/eNOS not fully defined
    • Contribution relative to SIRPα-mediated efferocytosis unclear
  17. 2024 High

    Demonstrated that CD47 expression is essential for adoptive T-cell persistence and that an engineered CD47 variant can protect cells from clearance while permitting macrophage recruitment, with TLR2 co-signaling identified as an additional CD47 partnership.

    Evidence CD47 KO in T cells, xenograft and adoptive transfer models, the CD47 Q31P/47E variant (CAR T study); CD47-TLR2 Co-IP, KO mice, and bactericidal assays (TLR2 study)

    PMID:38750365 PMID:39536084

    Open questions at the time
    • Long-term safety of engineered CD47 variants untested
    • Mechanism of CD47-TLR2 co-signaling to TSP-1 induction incompletely defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CD47's many context-specific functions—SIRPα inhibition, Fas-coupled apoptosis, TSP1-Gi/integrin signaling, autophagy, and TLR2 co-signaling—are mechanistically partitioned within a single receptor remains unresolved.
  • No unified structural model coupling the distinct ligand-engaged states
  • Lack of data on how cell type dictates which CD47 output dominates

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:0048018 receptor ligand activity 2
Localization
GO:0005886 plasma membrane 3
Pathway
R-HSA-168256 Immune System 3 R-HSA-162582 Signal Transduction 2 R-HSA-392499 Metabolism of proteins 2 R-HSA-5357801 Programmed Cell Death 1 R-HSA-9612973 Autophagy 1
Partners
FASSHP-1 (PTPN6)SHP-2 (PTPN11)SIRPASRCTHBS1TLR2TRIM21
Complex memberships
CD47-SIRPα signaling complexCD47-integrin-Gi protein supramolecular complex

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 CD47 functions as a 'marker of self' on red blood cells by binding to the inhibitory receptor SIRPα on splenic macrophages, thereby preventing phagocytic clearance; CD47-null mouse RBCs were rapidly cleared from the bloodstream by splenic red pulp macrophages, and this was rescued by CD47-SIRPα engagement. In vivo adoptive transfer of CD47-null vs. wild-type mouse RBCs; macrophage phagocytosis assays Science High 10856220
2001 CD47 (IAP) acts as a receptor for thrombospondin family members (via their C-terminal VVM motif), a ligand for SIRPα, and a component of a supramolecular complex with specific integrins, heterotrimeric G proteins, and cholesterol; CD47 agonist peptides initiate heterotrimeric Gi protein signaling that augments β1, β2, and β3 integrin functions. Biochemical reconstitution, peptide agonist assays, co-immunoprecipitation of complex components Trends in cell biology Medium 11306274
2005 CD47 associates with Fas (CD95) upon Fas activation and augments Fas-mediated apoptosis; Jurkat T cells lacking CD47 are relatively resistant to Fas-mediated death, and re-expression of CD47 rescues killing; CD47 deficiency impairs caspase activation, cytochrome c release, loss of mitochondrial membrane potential, and DNA cleavage downstream of Fas. CD47-knockout Jurkat cells, CD47 re-expression, co-immunoprecipitation of Fas and CD47, primary T cells from CD47-null mice The Journal of biological chemistry High 15917238
2005 Human SIRPα1 binds CD47 on human and pig RBCs but not mouse, rat, or cow RBCs, demonstrating species- and cell-type specificity; deglycosylation of SIRPα1 strengthens binding; low SIRPα copy numbers on phagocytes explain absence of RBC adhesion under physiological conditions; bone marrow-derived mesenchymal stem cells display CD47 but do not significantly bind soluble SIRPα1. SIRPα1 binding assay, atomic force microscopy, centrifugation-based adhesion assay, antibody inhibition Blood Medium 16291597
2009 SIRPα binds to protein tyrosine phosphatases SHP-1 and SHP-2 through its cytoplasmic region; CD47 binding to SIRPα constitutes a bidirectional cell-cell communication system important for regulating migration and phagocytosis; activating SIRPβ shows negligible CD47 binding despite extensive extracellular sequence similarity to SIRPα. Biochemical binding assays, structural analysis, functional phagocytosis assays Trends in cell biology Medium 19144521
2014 Cell rigidity and shape of a phagocytic target can override CD47's 'self' signaling by hyperactivating myosin-II at the phagocytic synapse; controlled stiffening of normal human RBCs does not compromise CD47-SIRPα interaction, but rigid RBC discocytes show maximal myosin-II activation that overcomes CD47 inhibitory signaling; shape (stomatocyte vs. discocyte) modulates how effectively CD47 inhibits phagocytosis. RBC stiffening manipulation, phagocytosis assays with macrophages, myosin-II activity measurements, CD47-SIRPα binding confirmed by antibody inhibition Blood Medium 25411427
2015 MYC oncogene directly binds the promoters of Cd47 and Pd-l1 genes to transcriptionally regulate their expression; MYC inactivation reduces CD47 and PD-L1 mRNA and protein; enforced expression of CD47 in MYC-inactivated tumors suppresses the antitumor immune response and allows continued tumor growth. ChIP of MYC at Cd47/Pd-l1 promoters, MYC inducible mouse tumor models, CD47 enforced expression rescue experiments, qRT-PCR, Western blot Science High 26966191
2015 CD47 blockade requires dendritic cell cross-priming of T cell responses (not macrophage phagocytosis) in syngeneic immunocompetent mouse tumor models; therapeutic effects are abrogated in T cell-deficient mice; antitumor effects require STING (but not MyD88 or TRIF) in CD11c+ cells, linking cytosolic DNA sensing to CD47 blockade activity. Syngeneic mouse tumor models, T cell-deficient mice, STING/MyD88/TRIF genetic knockouts, macrophage/DC depletion Nature medicine High 26322579
2012 CD47 deficiency or blockade activates autophagic flux in irradiated T cells and endothelial cells; this enhanced autophagy (evidenced by increased BECN1, ATG5, ATG7, LC3+ puncta, autophagosomes by EM, reduced p62) is necessary for the radioprotective effect of CD47 blockade; pharmacological or siRNA inhibition of autophagy selectively sensitizes CD47-deficient cells to radiation, and re-expression of CD47 reverses autophagy and restores radiosensitivity. CD47-null T cells, CD47 re-expression, siRNA/pharmacological autophagy inhibition, electron microscopy, flow cytometry, Western blot Autophagy High 22874555
2016 TNF-α drives upregulation of CD47 on diseased vascular cells in atherosclerosis, impairing efferocytosis; CD47-blocking antibodies restore macrophage-mediated phagocytic clearance of apoptotic vascular cells and ameliorate atherosclerosis in multiple mouse models. Multiple atherosclerosis mouse models, anti-CD47 antibody treatment, TNF-α mechanistic studies, efferocytosis assays Nature High 27437576
2018 CD47 on synapses protects them from excessive microglia-mediated pruning during development via CD47-SIRPα signaling; CD47-deficient mice show increased microglial engulfment of retinogeniculate inputs, reduced synapse numbers in dLGN, and increased functional pruning; CD47 is required for neuronal activity-dependent preferential protection of active inputs from microglial engulfment. CD47 knockout mice, microglial engulfment assays, electrophysiology, confocal imaging of retinogeniculate system Neuron High 30308165
2021 NK cell SIRPα is upregulated by IL-2 stimulation and interacts with target cell CD47 in a threshold-dependent manner, counteracting stimulatory signals (IL-2, CD16, NKG2D); elevated CD47 on target cells protects against SIRPα+ primary NK cells but not SIRPα- NK cell lines; SIRPα deficiency or antibody blockade increases NK cell killing capacity. NK cell SIRPα characterization, CD47-overexpressing target cells, SIRPα KO, antibody blockade, cytotoxicity assays The Journal of experimental medicine Medium 33416832
2022 Senescent cells upregulate CD47 coinciding with increased expression of CD47-modifying enzymes QPCT/L; this enhanced CD47 suppresses macrophage-mediated efferocytosis of both senescent cells and bystander apoptotic corpses (SCES) via the SIRPα-CD47-SHP-1 axis; SCES requires direct macrophage-senescent cell contact and is reversible by interfering with SIRPα-CD47-SHP-1 signaling or QPCT/L activity. Senescent fibroblast and epithelial cell models, efferocytosis assays, CD47/QPCT/L knockout and inhibition, contact-dependent assays, in vitro and in vivo senescence models The Journal of cell biology High 36459066
2023 EGFR activation induces c-Src binding to CD47, leading to c-Src-mediated CD47 Y288 phosphorylation; this phosphorylation inhibits TRIM21 (ubiquitin E3 ligase) binding to CD47, preventing TRIM21-mediated K99/102 polyubiquitylation and proteasomal degradation of CD47; CD47 Y288F knock-in reduces CD47 expression and increases macrophage phagocytosis, while CD47 K99/102R knock-in has opposite effects. Co-IP of c-Src and CD47, mutagenesis (Y288F and K99/102R knock-in), ubiquitylation assays, in vitro EGFR/c-Src kinase assays, phagocytosis assays, in vivo brain tumor models Advanced science High 37541303
2023 The CD47/SIRPα axis requires deneddylation of SHP2 for its downstream signaling: SHP2 is constitutively neddylated on K358 and K364 (maintaining autoinhibited conformation); upon CD47-liganded SIRPα activation, SENP8 deneddylates SHP2, enabling dephosphorylation of substrates at the phagocytic cup and inhibition of macrophage phagocytosis. Mass spectrometry identification of neddylation sites, mutagenesis of K358/K364, SENP8 siRNA/KO, phagocytosis assays, substrate dephosphorylation assays The Journal of clinical investigation High 36626230
2021 IFN-γ upregulates CD47 expression on cancer cells via the JAK1/STAT1/IRF1 signaling pathway; IFN-γ-induced CD47 surface expression strengthens CD47-SIRPα binding and decreases macrophage phagocytosis of cancer cells; JAK1/2 inhibition or siRNA silencing of JAK1, STAT1, or IRF1 reverses this effect. siRNA knockdown, JAK1/2 inhibitor (ruxolitinib), flow cytometry for surface CD47, phagocytosis assays, TCGA correlation analysis Translational oncology Medium 34171557
2022 Statins suppress CD47 expression by inhibiting nuclear translocation of NFκB1 p50, thereby reducing CD47-mediated anti-phagocytic signaling and amplifying the anti-atherosclerotic effects of CD47-SIRPα blockade in an additive manner. RNA sequencing, in vivo and in vitro statin treatment, NFκB1 p50 nuclear translocation assays, CD47 expression assays, phagocytosis assays, atherosclerosis mouse models Nature cardiovascular research Medium 35990913
2024 CD47 expression is critical for CAR T-cell survival in vivo; CD47-knockout CAR T cells are sensitized to macrophage-mediated phagocytosis and fail to expand and persist in vivo despite potent in vitro activity; a CD47 variant (CD47 Q31P/47E) engages SIRPα and resists blockade by anti-CD47 antibodies, protecting adoptively transferred T cells from macrophage clearance while enabling macrophage recruitment to tumors. CD47 knockout in T cells, xenograft models, in vitro phagocytosis assays, CD47 Q31P engineered variant, adoptive transfer experiments Nature High 38750365
2022 Extracellular vesicles (exosomes) released from CD47-overexpressing cells can transfer CD47 to the surface of recipient cells ('cross-dressing'), enabling the cross-dressed CD47 to interact with SIRPα and inhibit phagocytosis; however, unlike autogenous CD47, ligation of cross-dressed CD47 does not induce cell death. Exosome isolation, flow cytometry for surface CD47, SIRPα binding assays, phagocytosis assays, cell death assays comparing autogenous vs. cross-dressed CD47 eLife Medium 36454036
2022 Macrophage-specific SIRPα loss (but not global CD47 deletion) attenuates atherosclerosis by stimulating efferocytosis, reducing cholesterol accumulation, promoting lipid efflux, and inducing M2 polarization; conversely, myeloid cell-specific CD47 deletion inhibits efferocytosis, impairs cholesterol efflux, augments inflammation, and increases atherosclerosis, demonstrating cell-specific and opposite roles for CD47 vs. SIRPα in myeloid cells. Myeloid cell-specific and global conditional knockout mice, efferocytosis assays, cholesterol efflux assays, macrophage polarization, atherosclerosis mouse models Cardiovascular research High 34940829
2023 TSP1 inhibits lymphangiogenesis through CD47 activation in lymphatic endothelial cells (LECs): TSP1 inhibits VEGF-C-induced AKT and eNOS activation and attenuates NO production; CD47 silencing in LECs prevents TSP1's effects on lymphangiogenic AKT-eNOS signaling; LEC-specific Cd47 knockout mice show reduced atherosclerosis and increased lymphatic vessel density. LEC-specific Cd47 KO mice (Cd47ΔLEC), AAV8-PCSK9 atherosclerosis model, in vitro LEC assays, siRNA, Western blot for AKT/eNOS, Matrigel plug assay, immunostaining Arteriosclerosis, thrombosis, and vascular biology High 37259865
2024 CD47 associates with TLR2 in macrophages; CD47 blocking leads to decreased intracellular P. gingivalis survival dependent on bacterial major fimbriae; P. gingivalis infection induces increased TSP-1 expression and secretion, which broadly suppresses neutrophil bactericidal activity; CD47-TLR2 co-signaling induces TSP-1 to suppress neutrophil activity. Co-immunoprecipitation of CD47 and TLR2, anti-CD47 antibody blockade, CD47 knockout mice, intracellular survival assays, TSP-1 expression/secretion measurements Proceedings of the National Academy of Sciences Medium 39536084
2019 Thrombospondin-1 (TSP-1) signaling through CD47 inhibits Th17 differentiation and promotes Treg differentiation from CD4+ T cells; TSP-1 functions as a negative regulator of T cell activation, with CD47 as the receptor; siRNA knockdown of TSP-1 in T cells and moDCs confirms this negative regulatory role. Th17/Treg differentiation assays, exogenous TSP-1 treatment, siRNA knockdown of TSP-1, immunofluorescence, RT-PCR in patient samples Frontiers in immunology Medium 31214201

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 Role of CD47 as a marker of self on red blood cells. Science (New York, N.Y.) 1546 10856220
2016 MYC regulates the antitumor immune response through CD47 and PD-L1. Science (New York, N.Y.) 1156 26966191
2001 Integrin-associated protein (CD47) and its ligands. Trends in cell biology 721 11306274
2015 CD47 blockade triggers T cell-mediated destruction of immunogenic tumors. Nature medicine 654 26322579
2016 CD47-blocking antibodies restore phagocytosis and prevent atherosclerosis. Nature 564 27437576
2020 The CD47-SIRPα Immune Checkpoint. Immunity 554 32433947
2017 The CD47-SIRPα signaling axis as an innate immune checkpoint in cancer. Immunological reviews 445 28258703
2018 SIRPα-CD47 Immune Checkpoint Blockade in Anticancer Therapy. Trends in immunology 396 29336991
2009 Functions and molecular mechanisms of the CD47-SIRPalpha signalling pathway. Trends in cell biology 393 19144521
2018 CD47 Protects Synapses from Excess Microglia-Mediated Pruning during Development. Neuron 376 30308165
2020 Advances in Anti-Tumor Treatments Targeting the CD47/SIRPα Axis. Frontiers in immunology 308 32082311
2017 Cancer immunotherapy targeting the CD47/SIRPα axis. European journal of cancer (Oxford, England : 1990) 290 28286286
2021 Targeting CD47 for cancer immunotherapy. Journal of hematology & oncology 273 34717705
2022 Anti-GD2 synergizes with CD47 blockade to mediate tumor eradication. Nature medicine 198 35027753
2019 CD47: role in the immune system and application to cancer therapy. Cellular oncology (Dordrecht, Netherlands) 167 31485984
2021 The SIRPα-CD47 immune checkpoint in NK cells. The Journal of experimental medicine 165 33416832
2017 Is CD47 an innate immune checkpoint for tumor evasion? Journal of hematology & oncology 155 28077173
2021 CD47/SIRPα pathway mediates cancer immune escape and immunotherapy. International journal of biological sciences 154 34512146
2014 The CD47-SIRPα signalling system: its physiological roles and therapeutic application. Journal of biochemistry 144 24627525
2015 CD47 signaling pathways controlling cellular differentiation and responses to stress. Critical reviews in biochemistry and molecular biology 142 25708195
2022 Radiotherapy in combination with CD47 blockade elicits a macrophage-mediated abscopal effect. Nature cancer 137 36411318
2022 CD47-SIRPα-targeted therapeutics: status and prospects. Immuno-oncology technology 134 35754851
2020 Role of CD47 in Hematological Malignancies. Journal of hematology & oncology 133 32677994
2014 Cell rigidity and shape override CD47's "self"-signaling in phagocytosis by hyperactivating myosin-II. Blood 131 25411427
2005 Species- and cell type-specific interactions between CD47 and human SIRPalpha. Blood 126 16291597
2024 Engineered CD47 protects T cells for enhanced antitumour immunity. Nature 100 38750365
2022 CD47/SIRPα axis: bridging innate and adaptive immunity. Journal for immunotherapy of cancer 100 35831032
2009 Signal regulatory protein alpha (SIRPalpha)/CD47 interaction and function. Current opinion in immunology 100 19223164
2023 The landscape overview of CD47-based immunotherapy for hematological malignancies. Biomarker research 98 36726125
2022 CD47-SIRPα blocking-based immunotherapy: Current and prospective therapeutic strategies. Clinical and translational medicine 91 35908284
2020 Regulation of CD47 expression in cancer cells. Translational oncology 88 32920329
2019 Targeting CD47 in Sézary syndrome with SIRPαFc. Blood advances 88 30962222
2022 Senescent cells suppress macrophage-mediated corpse removal via upregulation of the CD47-QPCT/L axis. The Journal of cell biology 85 36459066
2021 Thrombospondin-1 CD47 Signalling: From Mechanisms to Medicine. International journal of molecular sciences 83 33920030
2012 CD47 deficiency confers cell and tissue radioprotection by activation of autophagy. Autophagy 81 22874555
2004 Role of CD47 in erythroid cells and in autoimmunity. Leukemia & lymphoma 81 15359629
2023 The application of HER2 and CD47 CAR-macrophage in ovarian cancer. Journal of translational medicine 78 37740183
2020 Just eat it: A review of CD47 and SIRP-α antagonism. Seminars in oncology 74 32517874
2022 Targeting CD47/SIRPα as a therapeutic strategy, where we are and where we are headed. Biomarker research 70 35418166
2023 Opportunities and challenges of CD47-targeted therapy in cancer immunotherapy. Oncology research 69 38188674
2005 CD47 augments Fas/CD95-mediated apoptosis. The Journal of biological chemistry 65 15917238
2018 Monoclonal anti-CD47 interference in red cell and platelet testing. Transfusion 64 30516833
2021 CD47 expression in gastric cancer clinical correlates and association with macrophage infiltration. Cancer immunology, immunotherapy : CII 61 33389016
2019 Checkpoint CD47 Function On Tumor Metastasis And Immune Therapy. OncoTargets and therapy 59 31806995
2023 SHP2 deneddylation mediates tumor immunosuppression in colon cancer via the CD47/SIRPα axis. The Journal of clinical investigation 58 36626230
2020 CD47: the next checkpoint target for cancer immunotherapy. Critical reviews in oncology/hematology 58 32535479
2015 SIRP/CD47 signaling in neurological disorders. Brain research 58 25795378
2020 The development of small-molecule inhibitors targeting CD47. Drug discovery today 57 33197622
2023 EGFR-Induced and c-Src-Mediated CD47 Phosphorylation Inhibits TRIM21-Dependent Polyubiquitylation and Degradation of CD47 to Promote Tumor Immune Evasion. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 56 37541303
2012 Therapeutic opportunities for targeting the ubiquitous cell surface receptor CD47. Expert opinion on therapeutic targets 55 23101472
2022 Role of CD47 in tumor immunity: a potential target for combination therapy. Scientific reports 54 35697717
2023 Deciphering the role of CD47 in cancer immunotherapy. Journal of advanced research 52 39167629
2022 The pleiotropic benefits of statins include the ability to reduce CD47 and amplify the effect of pro-efferocytic therapies in atherosclerosis. Nature cardiovascular research 52 35990913
2023 A nanodrug combining CD47 and sonodynamic therapy efficiently inhibits osteosarcoma deterioration. Journal of controlled release : official journal of the Controlled Release Society 51 36682726
2022 Loss of myeloid cell-specific SIRPα, but not CD47, attenuates inflammation and suppresses atherosclerosis. Cardiovascular research 49 34940829
1992 A new octopamine receptor class in locust nervous tissue, the octopamine 3 (OA3) receptor. Life sciences 49 1345878
2022 CD47 as a promising therapeutic target in oncology. Frontiers in immunology 47 36081498
2007 Evaluation of an ovine testis cell line (OA3.Ts) for propagation of capripoxvirus isolates and development of an immunostaining technique for viral plaque visualization. Journal of veterinary diagnostic investigation : official publication of the American Association of Veterinary Laboratory Diagnosticians, Inc 45 17823391
2021 Cancer Therapy Targeting CD47/SIRPα. Cancers 43 34944850
2019 Stealth functionalization of biomaterials and nanoparticles by CD47 mimicry. International journal of pharmaceutics 41 31421198
2024 Targeting the CD47/SIRPα pathway in malignancies: recent progress, difficulties and future perspectives. Frontiers in oncology 40 39040441
2023 Development and Characterization of Nanobody-Derived CD47 Theranostic Pairs in Solid Tumors. Research (Washington, D.C.) 39 36939440
2022 Ligufalimab, a novel anti-CD47 antibody with no hemagglutination demonstrates both monotherapy and combo antitumor activity. Journal for immunotherapy of cancer 38 36450383
2024 Cell autonomous functions of CD47 in regulating cellular plasticity and metabolic plasticity. Cell death and differentiation 37 39039207
2023 CD47 Activation by Thrombospondin-1 in Lymphatic Endothelial Cells Suppresses Lymphangiogenesis and Promotes Atherosclerosis. Arteriosclerosis, thrombosis, and vascular biology 37 37259865
2022 CD47: Beyond an immune checkpoint in cancer treatment. Biochimica et biophysica acta. Reviews on cancer 36 35931392
2019 Cancer cell-expressed SLAMF7 is not required for CD47-mediated phagocytosis. Nature communications 35 30710089
2019 CD47 promotes cell growth and motility in epithelial ovarian cancer. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 35 31493748
2022 Fatty Acids, CD36, Thrombospondin-1, and CD47 in Glioblastoma: Together and/or Separately? International journal of molecular sciences 34 35054787
2019 Concurrent Expression of CD47 and CD44 in Colorectal Cancer Promotes Malignancy. Pathobiology : journal of immunopathology, molecular and cellular biology 34 31132784
2022 Recent Advances of Tumor Therapy Based on the CD47-SIRPα Axis. Molecular pharmaceutics 33 35436123
2021 CD47 and thrombospondin-1 regulation of mitochondria, metabolism, and diabetes. American journal of physiology. Cell physiology 33 34106789
2021 Regulation of CD47 expression by interferon-gamma in cancer cells. Translational oncology 33 34171557
2020 CD47 prevents the elimination of diseased fibroblasts in scleroderma. JCI insight 32 32814713
2023 CD47 expression is critical for CAR T-cell survival in vivo. Journal for immunotherapy of cancer 30 36918226
2019 Increased lymphocyte activation and atherosclerosis in CD47-deficient mice. Scientific reports 30 31337788
2018 Insights into CD47/SIRPα axis-targeting tumor immunotherapy. Antibody therapeutics 30 34056543
2022 CD47 cross-dressing by extracellular vesicles expressing CD47 inhibits phagocytosis without transmitting cell death signals. eLife 29 36454036
2021 CD47 (Cluster of Differentiation 47). Atlas of genetics and cytogenetics in oncology and haematology 29 34707698
2016 Enhanced biocompatibility of CD47-functionalized vascular stents. Biomaterials 28 26914699
2024 Opportunities and challenges for anti-CD47 antibodies in hematological malignancies. Frontiers in immunology 27 38464520
2020 Clinicopathological significance of CD47 expression in hepatocellular carcinoma. Journal of clinical pathology 27 32576628
2017 Significance of CD47 expression in gastric cancer. Oncology letters 27 28693236
2021 CD47 in the Brain and Neurodegeneration: An Update on the Role in Neuroinflammatory Pathways. Molecules (Basel, Switzerland) 26 34203368
2020 CD47 as a Potential Target to Therapy for Infectious Diseases. Antibodies (Basel, Switzerland) 26 32882841
2016 Divergent modulation of normal and neoplastic stem cells by thrombospondin-1 and CD47 signaling. The international journal of biochemistry & cell biology 25 27163531
2021 Comparative sensitivity study of primary cells, vero, OA3.Ts and ESH-L cell lines to lumpy skin disease, sheeppox, and goatpox viruses detection and growth. Journal of virological methods 24 33864853
2020 Potential New Cancer Immunotherapy: Anti-CD47-SIRPα Antibodies. OncoTargets and therapy 24 33061420
2024 Biomimetic Nano-Degrader Based CD47-SIRPα Immune Checkpoint Inhibition Promotes Macrophage Efferocytosis for Cardiac Repair. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 23 38477522
2021 An antitumor peptide RS17-targeted CD47, design, synthesis, and antitumor activity. Cancer medicine 22 33629544
2016 The use of CD47-modified biomaterials to mitigate the immune response. Experimental biology and medicine (Maywood, N.J.) 22 27190273
2022 Checkpoint CD47 expression in classical Hodgkin lymphoma. British journal of haematology 21 35301709
2015 The effects of obesity on CD47 expression in erythrocytes. Cytometry. Part B, Clinical cytometry 21 25914268
2024 Hypoxia-induced ZEB1 promotes cervical cancer immune evasion by strengthening the CD47-SIRPα axis. Cell communication and signaling : CCS 20 38183060
2024 Tolerating CD47. Clinical and translational medicine 20 38362603
2024 m6A-methylated KCTD21-AS1 regulates macrophage phagocytosis through CD47 and cell autophagy through TIPR. Communications biology 20 38383737
2024 CD47 and thrombospondin-1 contribute to immune evasion by Porphyromonas gingivalis. Proceedings of the National Academy of Sciences of the United States of America 20 39536084
2022 Macrophage-associated immune checkpoint CD47 blocking ameliorates endometriosis. Molecular human reproduction 20 35404426
2019 Thrombospondin-1/CD47 Interaction Regulates Th17 and Treg Differentiation in Psoriasis. Frontiers in immunology 20 31214201
2024 Targeting HDAC6 improves anti-CD47 immunotherapy. Journal of experimental & clinical cancer research : CR 19 38414061

Missed literature

Know a paper Affinage missed for CD47? Flag it for the maintainers and the community.

No submissions yet.