Affinage

CD163

Scavenger receptor cysteine-rich type 1 protein M130 · UniProt Q86VB7

Length
1156 aa
Mass
125.5 kDa
Annotated
2026-04-28
100 papers in source corpus 26 papers cited in narrative 26 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CD163 is a macrophage-restricted scavenger receptor of the SRCR superfamily that functions as a central mediator of hemoglobin clearance, innate immune sensing, and tissue homeostasis. It serves as the primary endocytic receptor for haptoglobin–hemoglobin (Hp–Hb) complexes and free hemoglobin on macrophages, directing ligand internalization to lysosomes where heme oxygenase-1 catalyzes heme degradation into the anti-inflammatory metabolites CO, biliverdin, and iron, while simultaneously triggering secretion of IL-10 and other anti-inflammatory cytokines (PMID:11854028, PMID:16189277, PMID:15478309). Beyond hemoglobin scavenging, CD163 recognizes bacteria via its SRCR2 domain to promote proinflammatory cytokine production (PMID:18849484), scavenges HMGB1–haptoglobin complexes to limit sepsis-associated inflammation (PMID:27294203), neutralizes TWEAK to attenuate NF-κB–driven vascular inflammation (PMID:32924185), and drives protumoral macrophage activation through IL-6 production (PMID:29610117). CD163 also functions as the essential uncoating receptor for porcine reproductive and respiratory syndrome virus (PRRSV) through its SRCR5 and PSTII domains, as demonstrated by complete PRRSV resistance in CD163-knockout and domain-deletion pigs (PMID:32876563, PMID:38544785, PMID:38184111). ADAM17-mediated ectodomain shedding generates soluble CD163 that retains Hb-scavenging and TWEAK-neutralizing capacity, linking surface receptor density to both hemoglobin clearance and viral susceptibility (PMID:24965453, PMID:23589619).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1999 Medium

    Defining CD163 as a glucocorticoid- and cytokine-regulated macrophage surface molecule established the transcriptional framework for understanding its lineage-restricted expression and anti-inflammatory context.

    Evidence Monocyte culture with cytokines/dexamethasone, promoter analysis, mRNA/protein expression

    PMID:10725797

    Open questions at the time
    • Promoter GR binding sites identified by sequence only, not validated by ChIP
    • Functional significance of splice isoforms unclear
    • No in vivo validation of transcriptional regulation
  2. 2002 High

    Identification of CD163 as the endocytic receptor for haptoglobin–hemoglobin complexes resolved the long-standing question of how macrophages clear Hp–Hb from plasma during hemolysis, establishing the core physiological function of the receptor.

    Evidence Receptor-ligand binding assays and endocytosis experiments in macrophages, replicated across labs

    PMID:11854028 PMID:15478309

    Open questions at the time
    • Structural basis of Hp–Hb binding to CD163 not determined
    • Contribution of individual SRCR domains to Hp–Hb binding not mapped
  3. 2004 High

    Demonstrating that CD163-mediated Hp–Hb endocytosis leads to HO-1-catalyzed heme degradation into anti-inflammatory metabolites (CO, biliverdin) and triggers anti-inflammatory cytokine secretion established CD163 as an active immune-regulatory receptor, not merely a passive scavenger.

    Evidence Endocytosis experiments with HO-1 induction and cytokine secretion measurements

    PMID:15478309

    Open questions at the time
    • Signaling pathway from CD163 cytoplasmic tail to cytokine induction not defined
    • Relative contribution of CO vs. biliverdin to anti-inflammatory output unknown
  4. 2005 High

    Showing that CD163 binds and endocytoses free hemoglobin independently of haptoglobin at high concentrations, with competition at the same binding site, established a biphasic model of Hb clearance and extended receptor function beyond Hp-dependent scavenging.

    Evidence Competitive binding, endocytosis in CD163+ HEK293 and macrophages, CD163-negative controls, HO-1 mRNA readout

    PMID:16189277

    Open questions at the time
    • Affinity constants for free Hb vs. Hp–Hb binding not precisely compared
    • In vivo relevance of haptoglobin-independent Hb scavenging not tested
  5. 2007 High

    Functional screening identified CD163 as sufficient to confer PRRSV permissivity to non-permissive cells, revealing an unexpected viral receptor function and requiring the transmembrane-anchored full-length form.

    Evidence cDNA library screen, transient/stable transfection of non-permissive cells, splice variant analysis

    PMID:17494075

    Open questions at the time
    • Viral ligand on PRRSV not yet identified
    • Mechanism of CD163-dependent uncoating unknown
    • Role of specific SRCR domains not dissected
  6. 2008 High

    Mechanistic dissection of PRRSV entry showed that sialoadhesin mediates initial virus internalization while CD163 acts downstream as an intracellular uncoating receptor, resolving CD163's specific step in the viral entry pathway. Separately, CD163 was shown to function as a bacterial pattern recognition receptor through its SRCR2 domain.

    Evidence Temperature-block experiments, confocal imaging, sialoadhesin ± CD163 co-expression; bacterial binding assays with antibody blocking in primary monocytes

    PMID:18849484 PMID:19008379

    Open questions at the time
    • Structural mechanism of CD163-mediated viral uncoating unknown
    • Range of bacterial species recognized not fully characterized
    • Whether bacterial and viral ligand sites overlap not tested
  7. 2009 Medium

    Identification of CD163 as a scavenger receptor for TWEAK expanded its ligand repertoire beyond hemoglobin to include a TNF superfamily cytokine, while demonstration that CXCL4 downregulates CD163 via glycosaminoglycans provided the first mechanism of negative regulation by platelet-derived factors.

    Evidence TWEAK binding/internalization assays in CD163+ macrophages; CXCL4 downregulation with heparin neutralization and chlorate inhibition, HO-1 functional readout

    PMID:19473660 PMID:19910578

    Open questions at the time
    • TWEAK binding domain on CD163 not mapped
    • CXCL4 finding from single lab without independent confirmation
    • Physiological significance of TWEAK scavenging in vivo not established at this point
  8. 2012 Medium

    CD163 was shown to mediate Mycobacterium leprae uptake in monocytes through IL-10-dependent upregulation, and glucocorticoids were found to functionally upregulate CD163-dependent Hb scavenging in placental Hofbauer cells, extending CD163 function to pathogen entry and fetal-maternal hemoglobin homeostasis.

    Evidence Antibody blocking and HEK293 transfection for M. leprae uptake; western blot, flow cytometry, and Hb uptake assay in primary Hofbauer cells

    PMID:22851198 PMID:23142809

    Open questions at the time
    • M. leprae ligand for CD163 not identified
    • Whether CD163 mediates intracellular M. leprae survival unknown
    • Hofbauer cell findings not confirmed in vivo
  9. 2013 Medium

    Discovery that shed soluble CD163 sequesters free hemoglobin, suppresses its pseudoperoxidase activity, and is re-internalized via FcγR with IgG established an autocrine/paracrine recycling mechanism linking ectodomain shedding to active hemoglobin detoxification.

    Evidence Pseudoperoxidase assays, monocyte–endothelial coculture, endocytosis/recycling experiments, FcγR pathway studies

    PMID:23589619

    Open questions at the time
    • FcγR-dependent re-uptake mechanism not confirmed in vivo
    • Stoichiometry and kinetics of sCD163–Hb complex formation unclear
    • Single laboratory finding
  10. 2014 High

    Identifying ADAM17 as the metalloprotease responsible for CD163 ectodomain shedding, with direct demonstration that shedding regulates surface CD163 levels and PRRSV susceptibility, provided a molecular link between protease activity, receptor density, and viral infection.

    Evidence ADAM17 inhibitor, overexpression, and siRNA in Marc-145 cells and porcine alveolar macrophages with PRRSV infection readout

    PMID:24965453

    Open questions at the time
    • ADAM17 cleavage site on CD163 not mapped
    • Whether other ADAM family members contribute to shedding not excluded
    • Regulation of ADAM17-dependent shedding in physiological inflammation not studied
  11. 2016 High

    CD163 was established as an anti-inflammatory receptor for HMGB1–haptoglobin complexes through KO macrophage and genetic mouse studies showing that CD163 deficiency increases sepsis mortality, revealing a second damage-associated molecular pattern cleared by the Hp–CD163 axis. Separately, neuronal CD163 expression was shown to mediate iron-dependent Hb neurotoxicity.

    Evidence CD163-KO macrophages and mice in sepsis models; neuronal culture with Hb/Hp uptake and iron chelation

    PMID:27294203 PMID:27364920

    Open questions at the time
    • Whether HMGB1 and Hb compete for the same CD163 binding site unknown
    • Neuronal CD163 expression not confirmed in vivo in human brain tissue
  12. 2017 High

    CD163-KO mice showed biphasic effects after intracerebral hemorrhage — early benefit from reduced iron/Hb accumulation but late worsening with larger lesions — establishing that CD163's hemoglobin scavenging function has temporally distinct pro- and anti-inflammatory consequences in the brain.

    Evidence CD163-KO mouse ICH model with serial hematoma, iron, BBB, HO-1, and neurobehavior measurements

    PMID:28358264

    Open questions at the time
    • Cellular source of CD163 in the brain (resident microglia vs. infiltrating macrophages) not resolved
    • Whether temporal effects are dose-dependent or context-dependent unclear
  13. 2018 High

    CD163 was shown to be required for protumoral macrophage activation through IL-6 production (via KO, silencing, and rescue), and separately found to interact with casein kinase 2 to activate AKT/β-catenin signaling in glioma cells, revealing tumor-intrinsic and macrophage-extrinsic oncogenic roles.

    Evidence CD163-KO mice with sarcoma model, siRNA/rescue in macrophage–tumor coculture, IL-6 epistasis; Co-IP for CD163–CK2, pathway knockdown in glioma cells

    PMID:29610117 PMID:30258108

    Open questions at the time
    • CD163 ligand triggering macrophage IL-6 production not identified
    • CD163–CK2 interaction based on single Co-IP without reciprocal validation
    • Whether CD163 on tumor cells vs. macrophages drives glioma effects not fully resolved
  14. 2020 High

    CD163-knockout pigs were shown to be completely resistant to PRRSV-2, definitively establishing CD163 as an essential in vivo entry receptor. In parallel, CD163 was placed downstream of CCR4/ERK/Nrf2 in hematoma resolution, and soluble CD163 was shown to neutralize TWEAK-driven NF-κB activation and vascular inflammation in atherosclerosis.

    Evidence CRISPR KO pigs with PRRSV challenge; mouse ICH model with CD163 CRISPR KO and pathway inhibitors; ApoE/CD163 double-KO mice with recombinant CD163 rescue and TWEAK challenge

    PMID:32783091 PMID:32876563 PMID:32924185

    Open questions at the time
    • Whether CD163 KO pigs resist all PRRSV genotypes not yet tested
    • Direct transcriptional regulation of CD163 by Nrf2 not confirmed by ChIP
    • Whether TWEAK neutralization is the primary atheroprotective mechanism of sCD163 vs. Hb clearance unknown
  15. 2023 High

    Mapping PRRSV GP4 interaction to the SRCR5 domain and identifying critical residues (570–576 in SRCR5, Q797 in SRCR7) provided the first molecular-resolution understanding of how PRRSV engages CD163, enabling structure-based antiviral strategies. Separately, CD163-driven Hb/Hp-loaded macrophages were shown to inhibit vascular calcification through NF-κB-induced HAS expression in smooth muscle cells.

    Evidence BiFC, Kd measurement, site-directed mutagenesis with functional reconstitution; VSMC culture with macrophage supernatant, HAS knockdown, NF-κB inhibition in ApoE-/- mice

    PMID:36719758 PMID:37133376

    Open questions at the time
    • Crystal structure of SRCR5–GP4 complex not available
    • Relative contribution of SRCR5 vs. PSTII domain to uncoating unknown
    • Whether HAS induction is specific to M(Hb) macrophages or shared with other CD163 ligand-activated states unclear
  16. 2024 High

    Domain-specific deletions in pigs (exon 7/SRCR5 and exon 13/PSTII) independently conferred complete PRRSV resistance while preserving hemoglobin scavenging, resolving which domains are essential for viral uncoating versus physiological function. CD163+ macrophage-driven endothelial-to-mesenchymal transition via NF-κB/Snail was established as a mechanism of plaque progression.

    Evidence Gene-edited pigs with domain-specific deletions and PRRSV challenge; macrophage conditioned medium on HAECs, EndMT markers, CD163-KO ApoE-/- mice, scRNA-seq and human tissue

    PMID:38184111 PMID:38544785 PMID:38860377

    Open questions at the time
    • Whether SRCR5 deletion affects responses to non-PRRSV pathogens unknown
    • Signaling pathway linking CD163 ligation to NF-κB/Snail activation in endothelial cells not fully dissected
    • Long-term cardiovascular outcomes in CD163-KO models not reported

Open questions

Synthesis pass · forward-looking unresolved questions
  • The intracellular signaling pathway linking CD163 cytoplasmic domain engagement to downstream transcriptional responses (IL-6, IL-10, HO-1 induction) remains undefined, as does the structural basis of ligand discrimination among Hp–Hb, HMGB1, TWEAK, and bacteria.
  • No crystal or cryo-EM structure of CD163 with any ligand
  • Cytoplasmic tail signaling adaptors not identified
  • Whether CD163 functions as a monomer or oligomer during endocytosis unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0038024 cargo receptor activity 5 GO:0060089 molecular transducer activity 3 GO:0098772 molecular function regulator activity 2
Localization
GO:0005886 plasma membrane 4 GO:0005576 extracellular region 3 GO:0005764 lysosome 2 GO:0005768 endosome 1
Pathway
R-HSA-1643685 Disease 5 R-HSA-382551 Transport of small molecules 4 R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 3
Partners
ADAM17CSNK2A1HBBHMGB1HPSIGLEC1TNFSF12

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 CD163 was identified as the endocytic receptor that binds hemoglobin (Hb) in complex with haptoglobin (Hp), mediating removal of the Hp-Hb complex from plasma via receptor-mediated endocytosis in macrophages, leading to lysosomal degradation of the ligand and explaining haptoglobin depletion during intravascular hemolysis. Receptor-ligand binding assays, endocytosis experiments in macrophages The international journal of biochemistry & cell biology High 11854028 15478309
2005 CD163 functions as a scavenger receptor for native and chemically modified hemoglobins in the absence of haptoglobin: Hb interacts directly with CD163 via receptor-dependent endocytosis, inhibits Hb-Hp uptake (suggesting a common binding site), and induces heme oxygenase mRNA expression in CD163+ but not CD163- cells. Hp-complex formation critically enhances Hb uptake at low but not high ligand concentrations, supporting a biphasic model of macrophage Hb clearance. In vitro endocytosis assays in CD163+ HEK293 cells and human macrophages, competitive binding experiments, receptor-negative control cells, mRNA expression assays Blood High 16189277
2004 CD163-mediated endocytosis of haptoglobin-hemoglobin complexes leads to lysosomal Hp-Hb breakdown and heme oxygenase-catalyzed conversion of heme into anti-inflammatory metabolites (CO, biliverdin, iron), and CD163 directly induces intracellular signaling leading to secretion of anti-inflammatory cytokines. Cell biology assays, endocytosis experiments, cytokine secretion measurements Annals of medicine High 15478309
2008 CD163 functions as a macrophage pattern recognition receptor for both Gram-positive and Gram-negative bacteria; a previously identified cell-binding motif in the second scavenger domain (SRCR2) of CD163 mediates bacterial binding. Expression of CD163 in monocytic cells promotes bacteria-induced proinflammatory cytokine production, and antagonistic anti-CD163 antibodies potently inhibit cytokine production in freshly isolated human monocytes. Bacterial binding assays with CD163-expressing cells, antagonistic antibody experiments, cytokine production assays in primary human monocytes Blood High 18849484
2007 CD163 confers susceptibility to porcine reproductive and respiratory syndrome virus (PRRSV): direct functional screening identified CD163 as sufficient to render non-permissive cells PRRSV-permissive. Full-length CD163 with the C-terminal transmembrane anchor is required; splice variants lacking this domain do not provide PRRSV receptor function. cDNA expression library screening, transient transfection of non-permissive cell lines, stable cell line establishment, virus infectivity assays Journal of virology High 17494075
2008 Sialoadhesin and CD163 cooperate sequentially during PRRSV entry: sialoadhesin mediates virus internalization at the cell surface (active at 4°C), while CD163 acts downstream during virus uncoating after internalization (active at 37°C). Expression of sialoadhesin alone leads to PRRSV internalization without uncoating or productive infection; co-expression of both receptors restores productive infection and increases virus production 10–100-fold. Antibody blocking at 4°C vs. 37°C, confocal microscopy of PRRSV entry, non-permissive cells expressing sialoadhesin alone or together with CD163, virus production quantification The Journal of general virology High 19008379
2016 CD163 was identified as an antiinflammatory receptor for HMGB1-haptoglobin complexes. Haptoglobin binds HMGB1 and targets uptake through CD163; haptoglobin-HMGB1 complexes elicit production of heme oxygenase-1 and IL-10 in wild-type but not CD163-deficient macrophages. Genetic disruption of haptoglobin or CD163 significantly enhances mortality in mouse models of intra-abdominal sepsis. Co-immunoprecipitation/binding assays, CD163-deficient macrophages vs WT, genetic knockout mouse models, cytokine/enzyme production assays JCI insight High 27294203
1999 CD163 expression is transcriptionally induced by M-CSF, IL-10, and dexamethasone, and suppressed by LPS, IFN-γ, and GM-CSF/IL-4. Dexamethasone induction is mediated by glucocorticoid receptor binding sites in the proximal promoter. Multiple isoforms arise from alternative splicing and differ in cytoplasmic or extracellular domains, potentially affecting function. In vitro monocyte culture with cytokines/drugs, mRNA expression analysis, promoter analysis, genomic organization mapping Pathobiology Medium 10725797
2009 CD163-expressing macrophages can bind and internalize TWEAK (TNF-like weak inducer of apoptosis) protein, identifying CD163 as a scavenger receptor for soluble TWEAK. This interaction is proposed to decrease TWEAK plasma concentration. In vitro binding and internalization assays of exogenous TWEAK in cultured human CD163-expressing macrophages Atherosclerosis Medium 19473660
2009 CXCL4 (platelet factor 4) downregulates CD163 expression in human macrophages through binding to cell-surface glycosaminoglycans; heparin neutralizes the CXCL4 effect, and chlorate (which inhibits glycosaminoglycan synthesis) blocks CXCL4-dependent CD163 downregulation. Loss of CD163 renders macrophages unable to upregulate heme oxygenase-1 in response to hemoglobin-haptoglobin complexes. Flow cytometry, mRNA expression, heparin neutralization, chlorate inhibition of glycosaminoglycan synthesis, functional HO-1 induction assay Circulation research High 19910578
2013 CD163 directly suppresses hemoglobin pseudoperoxidase activity via an autocrine loop: membrane CD163 is shed as sCD163 which sequesters free Hb; the sCD163-Hb complex is endocytosed via FcγR with IgG into monocytes and recycled, restoring membrane CD163 homeostasis. In a paracrine manner, monocyte-derived sCD163 and IgG shuttle residual Hb into endothelial cells for detoxification. In vitro Hb pseudoperoxidase activity assays, ex vivo coculture of monocytes and endothelial cells, endocytosis and recycling experiments, FcγR pathway studies Journal of immunology Medium 23589619
2012 CD163 mediates uptake of Mycobacterium leprae (ML) in human monocytes: CD163 blockade reduced ML uptake in human monocytes, and HEK293 cells transfected with CD163 cDNA showed higher ML uptake than untransfected cells. ML-induced CD163 upregulation was IL-10-dependent (IL-10 blockade reduced CD163 expression), and increased CD163 expression contributed to augmented iron storage in lepromatous macrophages. CD163 antibody blocking, HEK293 transfection with CD163 cDNA, ML uptake assays, IL-10 blockade experiments, iron storage measurement European journal of immunology Medium 22851198
2014 ADAM17 (metalloprotease) mediates ectodomain shedding of CD163 from the cell surface, negatively regulating PRRSV entry: inhibition of ADAM17 upregulates membrane CD163 and enhances PRRSV infection, whereas ADAM17 overexpression reduces surface CD163 and PRRSV infection. siRNA knockdown of ADAM17 increases CD163 expression with a corresponding increase in PRRSV infection. ADAM17 inhibitor experiments, ADAM17 overexpression and siRNA knockdown, surface CD163 quantification, PRRSV infection assays in Marc-145 and porcine alveolar macrophages Journal of virology High 24965453
2018 CD163 is required for protumoral macrophage activation: silencing CD163 abrogates macrophage-induced tumor cell proliferation in coculture. In CD163-deficient mice, sarcoma tumor development is significantly reduced. CD163-deficient macrophages show suppressed production of IL-6 and CXCL2; overexpression of CD163 in CD163-deficient macrophages rescues IL-6 and CXCL2 production. IL-6 (but not CXCL2) silencing abrogates macrophage-induced tumor cell proliferation. CD163 siRNA silencing in coculture, CD163-knockout mice, CD163 overexpression rescue, IL-6/CXCL2 silencing epistasis Cancer research High 29610117
2018 CD163 interacts directly with casein kinase 2 (CK2) in glioma cells; CD163 silencing reduces AKT/GSK3β/β-catenin/cyclin D1 pathway activity via CK2, inhibiting cell cycle progression and proliferation of GBM cells. CD163 is upregulated in CD133+ glioma stem cells (GSCs) and its knockdown impairs GSC stemness via the CK2/AKT/GSK3β/β-catenin pathway. Co-immunoprecipitation demonstrating CD163-CK2 direct interaction, CD163 siRNA knockdown, pathway activity assays (AKT/GSK3β/β-catenin/cyclin D1), cell proliferation and stemness marker assays Oncogene Medium 30258108
2016 Neurons express the CD163 receptor and internalize Hb and Hb-Hp complexes; haptoglobin increases vulnerability of CD163-expressing neurons to hemoglobin by directing Hb uptake to CD163+ neurons while attenuating the protective ferritin response in CD163-negative glia. Neuronal Hb toxicity via CD163 is iron-dependent. Primary cortical cell cultures, CD163 immunostaining on neurons, Hb/Hb-Hp uptake assays, deferoxamine/chelator experiments demonstrating iron-dependent mechanism Journal of neurochemistry Medium 27364920
2017 CD163 deficiency in mice has temporally distinct effects after intracerebral hemorrhage: at 3 days, CD163-KO mice have less hematoma volume, less hemoglobin/iron accumulation, and less blood-brain barrier dysfunction; at 10 days, CD163-KO mice have larger lesions and increased iron/VEGF. This establishes that CD163 mediates hemoglobin scavenging in the brain with early detrimental (pro-inflammatory Hb retention is initially limited without the receptor driving early HO-1 conversion) and late anti-inflammatory/reparative roles. CD163 knockout mice, intracerebral hemorrhage model, hematoma volume measurement, hemoglobin/iron quantification, BBB integrity assays, HO-1 expression, neurobehavioral testing Journal of cerebral blood flow and metabolism High 28358264
2020 CD163 knockout pigs are completely resistant to genotype 2 PRRSV infection, directly establishing CD163 as an essential entry receptor for PRRSV in vivo. The absence of CD163 results in increased iron in muscle (consistent with loss of hemoglobin-haptoglobin scavenging function) but no impairment of meat production or reproductive performance. CRISPR/Cas9 double-knockout pigs, PRRSV challenge experiments, PCR and serology, iron measurement in muscle tissue eLife High 32876563
2012 Glucocorticoids (cortisol and dexamethasone) specifically upregulate CD163 protein and mRNA in placental Hofbauer cells (fetal macrophages), and dexamethasone treatment increases hemoglobin uptake by Hofbauer cells, demonstrating that GC-induced CD163 upregulation is functionally active in enhancing Hb scavenging. Western blotting, flow cytometry, real-time PCR, hemoglobin uptake functional assay in primary Hofbauer cells, placental explant cultures Endocrinology Medium 23142809
2020 CCR4 activation by recombinant CCL17 promotes hematoma resolution after intracerebral hemorrhage via the CCR4/ERK/Nrf2/CD163 signaling pathway; CRISPR knockout of CD163 abolishes the protective effects of rCCL17, placing CD163 downstream of CCR4/ERK/Nrf2 in this pathway. Mouse ICH model, recombinant CCL17 treatment, selective CCR4/Nrf2 inhibitors, CD163 CRISPR knockout (intracerebroventricular), western blot, immunofluorescence, neurobehavior Neurotherapeutics Medium 32783091
2024 CD163+ macrophages exposed to hemoglobin-haptoglobin complexes induce endothelial-to-mesenchymal transition (EndMT) in atherosclerotic plaques via NF-κB-mediated Snail transcription factor activation. In vitro, supernatants from Hb/Hp-exposed macrophages induce mesenchymal markers (transgelin, FSP-1) and reduce endothelial markers (VE-cadherin, CD31) in human aortic endothelial cells. CD163 deletion in ApoE-/- mice reduces EndMT and plaque progression. In vitro macrophage conditioned medium experiments on HAECs, western blot for EndMT markers, NF-κB/Snail pathway analysis, CD163-KO ApoE-/- mouse model, human coronary artery pathological analysis, single-cell RNA sequencing Circulation research High 38860377
2020 CD163 deficiency in ApoE-/- mice increases foam cell formation through upregulation of CD36 expression in M2-type macrophages, leading to more unstable atherosclerotic plaques with increased lipid, macrophage content, and pro-inflammatory cytokines. Recombinant CD163 neutralizes proatherogenic TWEAK effects by abolishing NF-κB activation, cytokine/metalloproteinase expression, and macrophage migration in vascular smooth muscle cells. ApoE/CD163 double-deficient mice, foam cell formation assays, CD36 expression analysis, recombinant CD163 administration, NF-κB activation assays, TWEAK challenge FASEB journal High 32924185
2023 CD163+ macrophages engulfing hemoglobin:haptoglobin complexes (M(Hb) macrophages) inhibit vascular calcification through NF-κB-induced transcription of hyaluronan synthase (HAS) in vascular smooth muscle cells; knocking down HAS attenuates the anticalcific effect, and NF-κB blockade reduces hyaluronan and increases vascular calcification in ApoE-/- mice. In vitro VSMC culture with M(Hb) macrophage supernatant, NF-κB inhibitor experiments, HAS knockdown, ApoE-/- mouse model with NF-κB blockade, immunostaining of human arteries JCI insight High 36719758
2023 PRRSV glycoprotein 4 (GP4) directly interacts with the SRCR5 domain of CD163; small molecules physically binding to CD163-SRCR5 (Kd 28–39 μM) block PRRSV infection. Specific residues in SRCR5 (570SXDVGXV576) and Q797 in SRCR7 are conformational epitopes critical for PRRSV invasion, as CD163 with mutated epitopes expressed in 3D4 cells fails to support PRRSV infection while wild-type CD163 restores it. BiFC protein-protein interaction screening, direct binding assays (Kd measurement), site-directed mutagenesis of CD163 epitopes, PRRSV infection assays in mutant vs. WT CD163-expressing cells Journal of virology High 37133376
2024 Deletion of CD163 exon 13 (encoding the PSTII domain) is sufficient to confer complete resistance to PRRSV-2 infection in pigs in vivo, without affecting CD163's physiological hemoglobin-scavenging function, establishing the PSTII domain as required for PRRSV uncoating/entry. Gene-edited pigs (exon 13 deletion), PRRSV-2 challenge experiment, PCR and serology, physiological assessment Antiviral research High 38184111
2024 Pigs with deletion of exon 7 of CD163 (removing the SRCR5 domain) are completely resistant to PRRSV infection across multiple breeding generations, with no detected differences in growth rate, health, meat composition, or reproductive performance, confirming the SRCR5 domain as essential for PRRSV receptor function. CRISPR-Cas9 gene editing, multi-generation breeding, PRRSV challenge, growth/meat/reproduction performance assessment Frontiers in genome editing High 38544785

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 CD163 and inflammation: biological, diagnostic, and therapeutic aspects. Antioxidants & redox signaling 478 22900885
2004 CD163: a regulated hemoglobin scavenger receptor with a role in the anti-inflammatory response. Annals of medicine 355 15478309
2005 The macrophage scavenger receptor CD163. Immunobiology 340 16164022
2008 The macrophage scavenger receptor CD163 functions as an innate immune sensor for bacteria. Blood 331 18849484
2011 Soluble CD163. Scandinavian journal of clinical and laboratory investigation 312 22060747
2020 Transcriptional and Functional Analysis of CD1c+ Human Dendritic Cells Identifies a CD163+ Subset Priming CD8+CD103+ T Cells. Immunity 282 32610077
2007 CD163 expression confers susceptibility to porcine reproductive and respiratory syndrome viruses. Journal of virology 281 17494075
2018 CD163+ macrophages promote angiogenesis and vascular permeability accompanied by inflammation in atherosclerosis. The Journal of clinical investigation 275 29457790
2010 A subpopulation of CD163-positive macrophages is classically activated in psoriasis. The Journal of investigative dermatology 237 20555352
2005 CD163 is the macrophage scavenger receptor for native and chemically modified hemoglobins in the absence of haptoglobin. Blood 237 16189277
2008 Sialoadhesin and CD163 join forces during entry of the porcine reproductive and respiratory syndrome virus. The Journal of general virology 211 19008379
2020 Targeting of CD163+ Macrophages in Inflammatory and Malignant Diseases. International journal of molecular sciences 198 32752088
2002 CD163: a signal receptor scavenging haptoglobin-hemoglobin complexes from plasma. The international journal of biochemistry & cell biology 182 11854028
2019 Specific targeting of CD163+ TAMs mobilizes inflammatory monocytes and promotes T cell-mediated tumor regression. The Journal of experimental medicine 180 31375534
2009 CXCL4 downregulates the atheroprotective hemoglobin receptor CD163 in human macrophages. Circulation research 140 19910578
2013 The haptoglobin-CD163-heme oxygenase-1 pathway for hemoglobin scavenging. Oxidative medicine and cellular longevity 139 23781295
2020 Macrophage Activation Markers, CD163 and CD206, in Acute-on-Chronic Liver Failure. Cells 131 32397365
2009 The CD163-expressing macrophages recognize and internalize TWEAK: potential consequences in atherosclerosis. Atherosclerosis 124 19473660
2020 CD163 and pAPN double-knockout pigs are resistant to PRRSV and TGEV and exhibit decreased susceptibility to PDCoV while maintaining normal production performance. eLife 121 32876563
2016 Urinary Soluble CD163 in Active Renal Vasculitis. Journal of the American Society of Nephrology : JASN 108 26940094
2004 Association of CD163+ macrophages and local production of soluble CD163 with decreased lymphocyte activation in spondylarthropathy synovitis. Arthritis and rheumatism 107 15146432
2011 Parenchymal accumulation of CD163+ macrophages/microglia in multiple sclerosis brains. Journal of neuroimmunology 102 21737148
2010 A brief review of CD163 and its role in PRRSV infection. Virus research 102 20655964
2012 Tumor-promoting macrophages induce the expression of the macrophage-specific receptor CD163 in malignant cells. International journal of cancer 95 22362417
2011 Differential expression of CD163 on monocyte subsets in healthy and HIV-1 infected individuals. PloS one 94 21625498
2020 Urinary Soluble CD163: a Novel Noninvasive Biomarker of Activity for Lupus Nephritis. Journal of the American Society of Nephrology : JASN 92 32300067
2005 Human monocyte CD163 expression inversely correlates with soluble CD163 plasma levels. Cytometry. Part B, Clinical cytometry 90 15624200
2016 Identification of CD163 as an antiinflammatory receptor for HMGB1-haptoglobin complexes. JCI insight 88 27294203
2018 CD163 Is Required for Protumoral Activation of Macrophages in Human and Murine Sarcoma. Cancer research 82 29610117
2007 Gating the radical hemoglobin to macrophages: the anti-inflammatory role of CD163, a scavenger receptor. Antioxidants & redox signaling 77 17508920
2019 Molecular and clinical characterization of CD163 expression via large-scale analysis in glioma. Oncoimmunology 74 31143523
2019 Coexpression of CD163 and CD141 identifies human circulating IL-10-producing dendritic cells (DC-10). Cellular & molecular immunology 67 30842629
2009 Scavenger receptor CD163 and its biological functions. Acta medica (Hradec Kralove) 66 19777868
2019 The number and localization of CD68+ and CD163+ macrophages in different stages of cutaneous melanoma. Melanoma research 65 30399061
1999 The scavenger receptor CD163: regulation, promoter structure and genomic organization. Pathobiology : journal of immunopathology, molecular and cellular biology 61 10725797
2021 Activated Hepatic Stellate Cells Induce Infiltration and Formation of CD163+ Macrophages via CCL2/CCR2 Pathway. Frontiers in medicine 59 33614685
2014 Modulation of CD163 expression by metalloprotease ADAM17 regulates porcine reproductive and respiratory syndrome virus entry. Journal of virology 59 24965453
2014 Monocyte/macrophage-derived soluble CD163: a novel biomarker in multiple myeloma. European journal of haematology 57 24612259
2012 CD163 favors Mycobacterium leprae survival and persistence by promoting anti-inflammatory pathways in lepromatous macrophages. European journal of immunology 57 22851198
2021 The TWEAK/Fn14/CD163 axis-implications for metabolic disease. Reviews in endocrine & metabolic disorders 55 34542797
2018 CD163, a novel therapeutic target, regulates the proliferation and stemness of glioma cells via casein kinase 2. Oncogene 51 30258108
2016 Haptoglobin increases the vulnerability of CD163-expressing neurons to hemoglobin. Journal of neurochemistry 49 27364920
2012 Glucocorticoids enhance CD163 expression in placental Hofbauer cells. Endocrinology 48 23142809
2022 Changes in CD163+, CD11b+, and CCR2+ peripheral monocytes relate to Parkinson's disease and cognition. Brain, behavior, and immunity 44 35026420
2017 The absence of the CD163 receptor has distinct temporal influences on intracerebral hemorrhage outcomes. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 44 28358264
2020 Recombinant CCL17 Enhances Hematoma Resolution and Activation of CCR4/ERK/Nrf2/CD163 Signaling Pathway After Intracerebral Hemorrhage in Mice. Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics 43 32783091
2015 Oleacein enhances anti-inflammatory activity of human macrophages by increasing CD163 receptor expression. Phytomedicine : international journal of phytotherapy and phytopharmacology 43 26655408
2014 CD163 expression was associated with angiogenesis and shortened survival in patients with uniformly treated classical Hodgkin lymphoma. PloS one 43 24489836
2015 A subset of CD163+ macrophages displays mixed polarizations in discoid lupus skin. Arthritis research & therapy 42 26568320
2015 Significance of CD163-Positive Macrophages in Proliferative Glomerulonephritis. The American journal of the medical sciences 39 26379042
2017 A possible interaction between periostin and CD163+ skin-resident macrophages in pemphigus vulgaris and bullous pemphigoid. Experimental dermatology 37 27501402
2021 Macrophage Activation Markers, Soluble CD163 and Mannose Receptor, in Liver Fibrosis. Frontiers in medicine 36 33490096
2015 CD163/Hemoglobin Oxygenase-1 Pathway Regulates Inflammation in Hematoma Surrounding Tissues after Intracerebral Hemorrhage. Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association 36 26403367
2024 CD163+ Macrophages Induce Endothelial-to-Mesenchymal Transition in Atheroma. Circulation research 35 38860377
2013 CD163 and IgG codefend against cytotoxic hemoglobin via autocrine and paracrine mechanisms. Journal of immunology (Baltimore, Md. : 1950) 35 23589619
2005 Functional expression of the CD163 scavenger receptor on acute myeloid leukemia cells of monocytic lineage. Journal of leukocyte biology 33 16368951
2004 In vitro differentiation of porcine blood CD163- and CD163+ monocytes into functional dendritic cells. Immunobiology 33 15481141
2024 Single-cell profiling reveals kidney CD163+ dendritic cell participation in human lupus nephritis. Annals of the rheumatic diseases 31 38290829
2012 CD163 expression is increased in the involved skin and sera of patients with systemic lupus erythematosus. European journal of dermatology : EJD 31 22576016
2020 CD163 deficiency increases foam cell formation and plaque progression in atherosclerotic mice. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 30 32924185
2023 CD163+ macrophages restrain vascular calcification, promoting the development of high-risk plaque. JCI insight 29 36719758
2018 Gestational diabetes mellitus is associated with increased CD163 expression and iron storage in the placenta. American journal of reproductive immunology (New York, N.Y. : 1989) 29 29984475
2015 Hemoglobin induces monocyte recruitment and CD163-macrophage polarization in abdominal aortic aneurysm. International journal of cardiology 29 26296046
2022 Molecular mechanism of CD163+ tumor-associated macrophage (TAM)-derived exosome-induced cisplatin resistance in ovarian cancer ascites. Annals of translational medicine 27 36267748
2020 Lipopolysaccharide Downregulates CD163 Expression to Inhibit PRRSV Infection via TLR4-NF-κB Pathway. Frontiers in microbiology 27 32269560
2014 CD14+CD16+ and CD14+CD163+ monocyte subpopulations in kidney allograft transplantation. BMC immunology 26 24499053
2009 Diagnostic value of CD163 in cutaneous spindle cell lesions. Journal of cutaneous pathology 26 19040468
2003 Biological variation of soluble CD163. Scandinavian journal of clinical and laboratory investigation 26 12729065
2024 The Role of Soluble CD163 (sCD163) in Human Physiology and Pathophysiology. Cells 25 39451197
2023 Identification of New Compounds against PRRSV Infection by Directly Targeting CD163. Journal of virology 25 37133376
2023 Ferroptosis of CD163+ tissue-infiltrating macrophages and CD10+ PC+ epithelial cells in lupus nephritis. Frontiers in immunology 25 37583695
2018 Macrophage CD163 expression in cerebrospinal fluid: association with subarachnoid hemorrhage outcome. Journal of neurosurgery 24 30028262
2006 Differential expression of monocyte CD163 in single- and dual-asthmatic responders during allergen-induced bronchoconstriction. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology 23 17177682
2022 Adaptation of African swine fever virus to porcine kidney cells stably expressing CD163 and Siglec1. Frontiers in immunology 22 36389805
2018 Identification of mannose receptor and CD163 as novel biomarkers for colorectal cancer. Cancer biomarkers : section A of Disease markers 22 29226859
2019 Role of PFKFB3 and CD163 in Oral Squamous Cell Carcinoma Angiogenesis. Current medical science 21 31209811
2019 CD163+ macrophages infiltration correlates with the immunosuppressive cytokine interleukin 10 expression in tongue leukoplakia. Clinical and experimental dental research 21 31890299
2015 Interpreting CD56+ and CD163+ infiltrates in early versus late renal transplant biopsies. American journal of nephrology 21 26087825
2011 Pulmonary haptoglobin and CD163 are functional immunoregulatory elements in the human lung. Respiration; international review of thoracic diseases 21 21860221
2022 Insights from Transcriptomics: CD163+ Profibrotic Lung Macrophages in COVID-19. American journal of respiratory cell and molecular biology 20 35675555
2021 Urinary Soluble CD163 Levels Predict IgA Nephropathy Remission Status. Frontiers in immunology 20 35003086
2024 Genetically modified pigs lacking CD163 PSTII-domain-coding exon 13 are completely resistant to PRRSV infection. Antiviral research 19 38184111
2022 CD163 and CD206 expression define distinct macrophage subsets involved in active ANCA-associated glomerulonephritis. Journal of autoimmunity 19 36183584
2021 Infiltration of CD163-, PD-L1- and FoxP3-positive cells adversely affects outcome in patients with mantle cell lymphoma independent of established risk factors. British journal of haematology 19 33686666
2022 CD163-Expressing Porcine Macrophages Support NADC30-like and NADC34-like PRRSV Infections. Viruses 18 36146862
2024 Pigs lacking the SRCR5 domain of CD163 protein demonstrate heritable resistance to the PRRS virus and no changes in animal performance from birth to maturity. Frontiers in genome editing 17 38544785
2022 Urine Soluble CD163 Is a Promising Biomarker for the Diagnosis and Evaluation of Lupus Nephritis. Frontiers in immunology 17 35911758
2022 Recent advances in inhibition of porcine reproductive and respiratory syndrome virus through targeting CD163. Frontiers in microbiology 17 36187992
2023 The clinical utility of CD163 in viral diseases. Clinica chimica acta; international journal of clinical chemistry 16 36740088
2022 TREM2 and CD163 Ameliorate Microglia-Mediated Inflammatory Environment in the Aging Brain. Journal of molecular neuroscience : MN 16 35306602
2020 CD163 Antibodies Inhibit PRRSV Infection via Receptor Blocking and Transcription Suppression. Vaccines 16 33050150
2023 Hepatocellular carcinoma progression promoted by 5-lipoxygenase activity in CD163(+) tumor-associated macrophages. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 15 36966664
2020 Circulating extracellular vesicle-associated CD163 and CD206 in multiple myeloma. European journal of haematology 15 31855290
2019 The significance of CD163-expressing macrophages in asthma. Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology 15 31152786
2024 Role of CD163 in PRRSV infection. Virology 14 39423600
2024 Imaging of tumor-associated macrophage dynamics during immunotherapy using a CD163-specific nanobody-based immunotracer. Proceedings of the National Academy of Sciences of the United States of America 14 39693339
2015 Drug Trafficking into Macrophages via the Endocytotic Receptor CD163. Membranes 14 26111002
2024 Development of a CD163-Targeted PET Radiotracer That Images Resident Macrophages in Atherosclerosis. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 13 38548349
2023 Relevance of TMPRSS2, CD163/CD206, and CD33 in clinical severity stratification of COVID-19. Frontiers in immunology 13 36969980
2021 Dexamethasone enhances CD163 expression in porcine IPKM immortalized macrophages. In vitro cellular & developmental biology. Animal 13 33447967