Affinage

C3AR1

C3a anaphylatoxin chemotactic receptor · UniProt Q16581

Length
482 aa
Mass
53.9 kDa
Annotated
2026-04-28
100 papers in source corpus 41 papers cited in narrative 41 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

C3AR1 encodes a seven-transmembrane Gi/o/z-coupled GPCR that senses complement fragment C3a and the neuropeptide TLQP-21, transducing signals through PI3K/Akt/mTOR, ERK, Ca²⁺ mobilization, STAT3, and β-arrestin–dependent internalization to regulate immune cell activation, hemostasis, neuroinflammation, and metabolism (PMID:8765043, PMID:38072064, PMID:23263555, PMID:30415998). In innate and adaptive immunity, C3aR1 on dendritic cells upregulates MHC/costimulatory molecules for T cell priming, drives CD8⁺ T cell proliferation via mTOR/T-bet, promotes Th17 differentiation and B cell class-switch recombination, coordinates actin-dependent phagosomal capture of pathogenic fungi in macrophages, and activates Rap1b in platelets to regulate thrombus formation (PMID:18056835, PMID:30565852, PMID:31217324, PMID:36174103, PMID:29802205). In the central nervous system, microglial C3aR1 sustains reactive glial states in tauopathy through STAT3, governs a HIF-1α–driven metabolic–lipid axis that impairs Aβ phagocytosis in Alzheimer's disease, modulates synaptic pruning, and controls glutamatergic neuronal excitability in the prefrontal cortex (PMID:30415998, PMID:37317973, PMID:35715851, PMID:38641040). In adipose tissue, C3aR1 enhances β-adrenergic–induced lipolysis through Ca²⁺/ERK/HSL and regulates adaptive thermogenesis in a sexually dimorphic manner (PMID:28123945, PMID:38713526).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1996 High

    Cloning of C3aR established it as a 482-residue GPCR with an unusually large second extracellular loop that couples to G proteins to transduce C3a signals, answering the fundamental question of the molecular identity of the C3a receptor.

    Evidence Expression cloning from U-937 cells, radioligand binding and phosphoinositide hydrolysis in transfected HEK-293 and CHO cells

    PMID:8765043

    Open questions at the time
    • Endogenous G protein coupling specificity not determined
    • Downstream signaling cascades beyond phosphoinositide hydrolysis unknown
    • Three-dimensional structure unresolved
  2. 1999 High

    Identification of Arg331 as the essential transmembrane ligand-binding residue and GRK2/3/5/6 as the kinases mediating agonist-induced receptor desensitization resolved how C3aR recognizes C3a and how signaling is terminated.

    Evidence Site-directed mutagenesis with radioligand binding; GRK overexpression/inhibition with phosphorylation and PLC assays in RBL, COS-7, and HMC-1 cells

    PMID:10491297 PMID:10508278

    Open questions at the time
    • Full complement of phosphorylation sites not mapped
    • β-arrestin involvement in internalization not yet demonstrated
    • Whether the large EC loop contributes to binding affinity or selectivity remained unclear
  3. 2003 High

    Demonstrating that C3aR on hematopoietic cells retains stem/progenitor cells in bone marrow by enhancing SDF-1 responsiveness established the first non-inflammatory physiological role for C3aR in hematopoiesis.

    Evidence G-CSF mobilization assays in C3⁻/⁻ and C3aR⁻/⁻ mice, bone marrow chimeras, SB290157 pharmacology

    PMID:14604969

    Open questions at the time
    • Intracellular signaling linking C3aR to SDF-1 sensitization not delineated
    • Note: SB290157 later shown to be a C3aR agonist, complicating pharmacological interpretation
  4. 2007 High

    Showing that DC-intrinsic C3aR signaling upregulates MHC and costimulatory molecules for effective T cell priming established C3aR as a bridge between innate complement activation and adaptive immunity.

    Evidence C3aR⁻/⁻ DC allostimulation assays, skin allograft rejection model, flow cytometry

    PMID:18056835

    Open questions at the time
    • Exact signaling pathway within DCs not defined
    • Whether C3aR acts similarly in tolerogenic DC contexts unknown
  5. 2012 High

    Establishing that cessation of C3aR/C5aR signaling in CD4⁺ T cells triggers PI3Kγ/Akt/mTOR collapse and autoinductive TGF-β1–driven Foxp3⁺ iTreg induction defined C3aR as a tonic suppressor of regulatory T cell differentiation.

    Evidence C3aR/C5aR antagonism and KO in T cell cultures, PI3K/Akt/mTOR and Foxp3 assays, autoimmune disease models

    PMID:23263555

    Open questions at the time
    • Relative contributions of C3aR versus C5aR not fully dissected
    • Whether this mechanism operates in all tissue microenvironments unclear
  6. 2013 High

    Identification of C3aR1 as the receptor for VGF-derived TLQP-21 via an unbiased transcriptomic screen revealed that C3aR1 is a dual-ligand GPCR with functions extending beyond complement.

    Evidence Genome-wide RNAseq of responsive CHO-K1 cells, siRNA knockdown, pertussis toxin sensitivity, macrophage migration assay

    PMID:23940034

    Open questions at the time
    • Structural basis of TLQP-21 versus C3a recognition at C3aR not determined
    • Physiological contexts where TLQP-21/C3aR signaling dominates over C3a/C3aR not established
  7. 2014 High

    Structural characterization of TLQP-21 binding and functional dissection of C3aR's anti-apoptotic role during Listeria infection expanded understanding of ligand recognition and protective immune functions.

    Evidence NMR of TLQP-21, mutagenesis of C-terminal residues; C3aR⁻/⁻ mice infected with L. monocytogenes, Fas/Bcl-2/caspase-3 analysis

    PMID:24981453 PMID:25456411

    Open questions at the time
    • Anti-apoptotic signaling cascade downstream of C3aR not fully mapped
    • Whether TLQP-21 and C3a compete for the same binding site unclear
  8. 2016 High

    Two studies showed C3aR enhances β-adrenergic lipolysis via Ca²⁺/ERK/HSL in adipocytes and drives neutrophil NETosis linking complement to coagulation in tumorigenesis, revealing tissue-specific effector pathways.

    Evidence 3T3-L1 adipocyte assays with C3aR1⁻/⁻ and β-AR⁻/⁻ mice; mouse intestinal tumor models with NET quantification and coagulation assays

    PMID:26996437 PMID:28123945

    Open questions at the time
    • Whether lipolytic and NET pathways share common proximal signaling steps unknown
    • Biased agonism at C3aR in these contexts not explored
  9. 2017 High

    Discovery that C3aR drives intestinal stem cell expansion through Wnt and potentiates glucose-stimulated insulin secretion in β-cells extended C3aR's roles to tissue regeneration and metabolic hormone regulation.

    Evidence Intestinal organoids from C3⁻/⁻ and C3aR1⁻/⁻ mice with Lgr5 reporters; β-arrestin and insulin secretion assays in primary human/mouse islets

    PMID:28921001 PMID:28928734

    Open questions at the time
    • Mechanism linking C3aR to Wnt pathway activation not defined
    • Whether islet C3aR engagement is paracrine or autocrine not fully resolved
  10. 2018 High

    Identification of Rap1b as the platelet C3aR effector for thrombus formation and STAT3 as the microglial C3aR effector sustaining neuroinflammatory glial states in tauopathy established cell-type–specific downstream signaling nodes.

    Evidence Platelet-specific reconstitution in C3aR⁻/⁻ mice with nano-LC-MS/MS for Rap1b; C3ar1⁻/⁻ × PS19 tauopathy mice with RNA-seq and STAT3 analysis

    PMID:29802205 PMID:30415998

    Open questions at the time
    • How C3aR activates Rap1b (direct vs. intermediate) not determined
    • Whether STAT3 activation is Gi-dependent or β-arrestin-dependent in microglia not distinguished
  11. 2019 High

    Multiple studies demonstrated C3aR's engagement with PTEN to antagonize CXCR2-driven neutrophil mobilization, physical complex formation with VEGFR2/PDGFR/EGFR requiring IL-6R-gp130 co-signaling, T cell-intrinsic mTOR/T-bet activation for CD8⁺ expansion, and B2 cell-autonomous class-switch recombination—collectively establishing C3aR as a signaling integrator across diverse cellular contexts.

    Evidence C3aR1⁻/⁻ SCI models with PTEN pathway analysis; Co-IP/BRET/confocal for VEGFR2 complex; adoptive transfers of C3ar1⁻/⁻ T cells in cardiac allografts; C3ar1⁻/⁻ OVA immunization with B cell reconstitution

    PMID:30565852 PMID:30765465 PMID:31045582 PMID:31217324

    Open questions at the time
    • Structural basis of the C3aR-VEGFR2-gp130 complex not resolved
    • How C3aR-PTEN interaction is spatially organized in neutrophils unknown
    • Relative importance of T cell-intrinsic vs. DC-mediated C3aR in vivo not quantified
  12. 2020 High

    Demonstrating that TLQP-21 and C3a super-agonist induce overlapping transcriptomic changes in microglia that enhance motility and phagocytosis confirmed C3aR1 as a shared receptor mediating neuropeptide and complement-driven microglial activation.

    Evidence RNA-seq of C3aR1⁻/⁻ vs. WT primary microglia, phagocytosis/migration assays, intracerebroventricular TLQP-21 in 5xFAD mice

    PMID:31924226

    Open questions at the time
    • Whether TLQP-21 and C3a produce distinct signaling biases in microglia not fully resolved
    • Physiological TLQP-21 concentrations in brain parenchyma not established
  13. 2021 High

    Systematic genetic dissection showed that lectin-pathway-generated C3a signals specifically through C3aR (not C5aR1/C5aR2) to skew tumor-associated macrophages toward immunosuppression in sarcoma, while SB290157 was unmasked as a C3aR agonist whose apparent antagonism arises from β-arrestin-mediated internalization—fundamentally revising pharmacological interpretations of prior studies.

    Evidence Systematic KO panel (C3, MBL, C4, C1q, factor B, C3aR, C5aR1, C5aR2) in transplanted sarcoma; β-arrestin recruitment/internalization assays for SB290157 in primary macrophages

    PMID:33551801 PMID:34505065

    Open questions at the time
    • How many prior SB290157-based conclusions require reinterpretation not catalogued
    • Whether C3aR-specific antagonists free of agonist activity exist not established
  14. 2022 High

    A CRISPR genome-scale screen identified C3aR as selectively required for macrophage phagosomal capture of pathogenic fungi via actin-dependent membrane protrusions, revealing a pathogen-specific innate immune function distinct from general phagocytosis.

    Evidence Genome-scale CRISPR screen in macrophages, C3aR⁻/⁻ validation, live imaging of phagosome formation with Histoplasma/Candida/Coccidioides

    PMID:36174103

    Open questions at the time
    • Fungal ligand or opsonin that triggers phagosomal C3aR not identified
    • Whether C3aR phagosomal localization requires EMC-dependent trafficking not fully resolved
  15. 2023 High

    Cryo-EM structures of C3a-bound and apo C3aR revealed a unique anaphylatoxin recognition mode distinct from chemokine receptors, and comprehensive G protein coupling profiling established Gi/o/z preference with ligand-dependent biased agonism between C3a and TLQP-21, resolving long-standing questions about receptor activation and selectivity.

    Evidence Cryo-EM/crystal structures with mutagenesis; BRET G protein coupling, β-arrestin recruitment, internalization assays across multiple cell types

    PMID:37169960 PMID:38072064

    Open questions at the time
    • Structure of TLQP-21–bound C3aR not determined
    • Structural basis for β-arrestin-biased versus G protein-biased signaling not resolved
  16. 2023 High

    Microglial C3aR deletion rescued lipid dysregulation and phagocytic dysfunction in AD via suppression of a HIF-1α–driven metabolic axis, while C3aR was identified as the primary mediator of podocyte injury in membranous nephropathy over MAC—extending C3aR's pathogenic roles to metabolic reprogramming and kidney disease.

    Evidence C3ar1-KO × APP-KI mice with lipid profiling, HIF-1α analysis, phagocytosis assays; human podocyte glomerulus-on-a-chip with C3AR siRNA, mouse MN model

    PMID:37317973 PMID:38227377

    Open questions at the time
    • How C3aR activates HIF-1α in microglia not mechanistically defined
    • Whether C3aR-driven podocyte injury involves the same STAT3 or ERK pathways as other cell types unknown
  17. 2024 High

    C3aR was shown to regulate glutamatergic neuronal excitability in the prefrontal cortex, control sexually dimorphic adaptive thermogenesis in adipocytes, promote ERK-dependent AML cell survival as a targetable surface marker on NPM1-mutated leukemic stem cells, and modulate GSK3β-dependent α-synuclein pathology—demonstrating the breadth of cell-type–specific C3aR functions.

    Evidence C3aR KO with viral rescue and electrophysiology in mPFC; adipocyte-specific C3aR1 KO with sex-stratified metabolic phenotyping; flow cytometry screen of 362 markers on AML cells with ERK assays and anti-C3AR antibody NK killing; α-syn PFF models with GSK3β analysis

    PMID:36383712 PMID:38641040 PMID:38713526 PMID:39288893

    Open questions at the time
    • How C3aR modulates ion channel properties in glutamatergic neurons unknown
    • Mechanism of sexual dimorphism in adipocyte C3aR1 thermogenic signaling not defined
    • Whether anti-C3AR antibodies are effective in vivo in AML not demonstrated

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of TLQP-21 binding and biased agonism at C3aR, the molecular mechanism by which C3aR activates HIF-1α in microglia, how phagosomal C3aR recognizes fungal pathogens, the identity of downstream ion channel targets in neurons, and whether C3aR-selective antagonists devoid of agonist activity can be developed for therapeutic use.
  • Structure of TLQP-21–C3aR complex not determined
  • Mechanism of C3aR-HIF-1α coupling in microglia unknown
  • In vivo therapeutic potential of anti-C3AR antibodies in AML not tested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 3 GO:0098772 molecular function regulator activity 2
Localization
GO:0005886 plasma membrane 3 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-168256 Immune System 7 R-HSA-162582 Signal Transduction 6 R-HSA-1430728 Metabolism 3 R-HSA-109582 Hemostasis 1
Partners
C3AGRK2GRK3LFA-1RAP1BSTAT3TLQP-21VEGFR2

Evidence

Reading pass · 41 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 Human C3aR was cloned from U-937 cells and identified as a 482-residue GPCR with seven transmembrane helices and an unusually large second extracellular loop (~175 residues). Transfection of HEK-293 cells conferred specific C3a binding; co-transfection with Gα-16 in CHO cells enabled functional C3a-induced phosphoinositide hydrolysis, demonstrating G protein-coupled signaling. Expression cloning, radioligand binding, phosphoinositide hydrolysis assay in transfected cells European journal of immunology High 8765043
1999 Agonist-induced desensitization of C3aR involves rapid phosphorylation on serine and threonine residues (not tyrosine) by G protein-coupled receptor kinases (GRK2, GRK3, GRK5, GRK6). Overexpression of GRKs enhanced C3a-induced C3aR phosphorylation 1.5–1.9-fold and differentially reduced phospholipase C activity; antibody-mediated inhibition of endogenous GRK2/3 blocked C3aR phosphorylation. Endogenously expressed C3aR in HMC-1 mast cells also undergoes agonist-induced phosphorylation. Phosphorylation assays in RBL cells and COS-7, GRK overexpression/inhibition, phosphoamino acid analysis European journal of immunology High 10508278
1999 An essential C3a ligand-binding site resides in the transmembrane core of guinea pig C3aR, not in the large extracellular loop. Mutation of Arg331 (in transmembrane region) to Ala or Gln completely abolished C3a binding, whereas mutations of Asp182, Asp309, Asp310, and large EC loop deletions did not eliminate binding. Site-directed mutagenesis, competitive radioligand binding assay Biochemical and biophysical research communications High 10491297
2003 The C3a-C3aR axis retains hematopoietic stem/progenitor cells (HSPCs) in bone marrow by increasing their responsiveness to SDF-1, thereby counteracting G-CSF-induced mobilization. C3-/- and C3aR-/- mice showed significantly enhanced G-CSF-induced HSPC mobilization. Chimeric mouse experiments revealed that C3aR deficiency on graft-derived (hematopoietic) cells, not host stromal cells, is responsible for increased mobilization. G-CSF mobilization in C3-/- and C3aR-/- mice, bone marrow chimeras, pharmacological C3aR antagonism (SB290157) Blood High 14604969
2007 C3aR signaling on dendritic cells (DCs) is required for upregulating MHC and costimulatory molecule surface expression and for effective T cell priming against alloantigens. DCs lacking C3aR or treated with C3aR antagonist showed defective alloantigen-specific T cell priming and impaired skin allograft rejection. The alternative complement pathway (factor B-dependent, C4-independent) contributes C3a for this DC-autonomous allostimulation. C3aR-/- DC allostimulation assays, skin allograft rejection model, MHC/costimulatory molecule flow cytometry Blood High 18056835
2009 C3aR on HSPCs promotes their engraftment by augmenting matrix metalloprotease-9 (MMP-9) secretion and cell adhesion to stroma. C3aR-/- HSPCs showed delayed platelet/leukocyte recovery, reduced CFU-spleen formation, and decreased BM engraftment; they secreted less MMP-9 and had impaired stromal adhesion despite retaining C3a-enhanced SDF-1 responsiveness. Transplantation of C3aR-/- HSPCs, MMP-9 secretion assays, stromal adhesion assays, human CD34+ cord blood with SB290157 in NOD/SCID mice Leukemia High 19357704
2012 Absence of C3aR and C5aR signaling into CD4+ T cells leads to cessation of PI3Kγ/Akt/mTOR signaling, increased PKA activity, initiation of autoinductive TGF-β1 signaling, and induction of Foxp3+ regulatory T cells (iTreg). Endogenous TGF-β1 suppresses C3aR/C5aR signaling by preventing C3a/C5a production and upregulating the decoy receptor C5L2. C3aR/C5aR antagonism and KO in T cell cultures, PI3K/Akt/mTOR signaling assays, Foxp3 induction assays, autoimmune disease suppression Nature immunology High 23263555
2013 C3AR1 (C3aR1) was identified as the receptor mediating TLQP-21 (a VGF-derived peptide) signaling in rodent CHO-K1 cells. Identification used genome-wide transcriptome sequencing of responsive cells, followed by validation with receptor-selective antagonists and siRNA knockdown. TLQP-21 signaling via C3AR1 is pertussis toxin-sensitive (Gi-coupled) and promotes RAW264.7 macrophage migration. Genome-wide RNAseq, siRNA knockdown, receptor antagonists, pertussis toxin sensitivity assay, cell migration assay The Journal of biological chemistry High 23940034
2014 TLQP-21 is intrinsically disordered and undergoes a disorder-to-order transition adopting an α-helical conformation upon binding cells expressing C3aR1. The C-terminus is critical for receptor activation: a single R21A mutation or C-terminal amidation abolishes function. Human TLQP-21 (S20A substitution) activates human C3aR1 with lower potency than the rodent sequence. NMR/structural analysis, site-directed mutagenesis of TLQP-21, functional cell-based assays Structure High 25456411
2014 C3aR signaling protects myeloid and lymphoid cells from Listeria monocytogenes-induced apoptosis by suppressing Fas expression and caspase-3 activity while increasing Bcl-2 expression. C3aR-/- mice had increased bacterial burden, reduced survival, and increased TUNEL+ cells with elevated active caspase-3 and Fas, reduced Bcl-2, in spleen. Systemic L. monocytogenes infection of C3aR-/- mice, TUNEL staining, caspase-3/Fas/Bcl-2 Western blot/immunostaining Journal of immunology High 24981453
2016 C3aR-dependent NETosis (neutrophil extracellular trap formation) on neutrophils links complement activation triggered by circulating LPS to coagulation induction and N2 (pro-tumorigenic) neutrophil polarization in intestinal tumorigenesis. Increased circulating LPS upregulates C3aR on neutrophils, activating complement cascade leading to NETosis and coagulation. Mouse intestinal tumorigenesis models, neutrophil phenotyping, NET quantification, coagulation assays, complement pathway analysis Nature communications High 26996437
2016 TLQP-21 does not directly induce lipolysis but enhances β-adrenergic receptor-induced lipolysis through C3aR1, requiring Ca2+ mobilization and ERK-dependent activation of Hormone Sensitive Lipase (HSL). In vivo, chronic peripheral TLQP-21 reduces fat mass in diet-induced obese mice via β-adrenergic and C3aR1 co-activation. 3T3-L1 adipocyte assays, genetic KO (C3aR1-/- and β-AR-deficient mice), Ca2+ mobilization, ERK/HSL phosphorylation, in vivo lipolysis Molecular metabolism High 28123945
2017 C3aR1 expressed on surface of intestinal cells mediates C3a-driven intestinal stem cell expansion and organoid formation through Wnt signaling. C3- and C3aR1-deficient mice showed significantly reduced organoid formation; C3a promoted organoid growth and Lgr5/Ki67 expression in C3-deficient but not C3aR1-deficient mice, confirming receptor dependency. Intestinal organoid assays, C3-/- and C3aR1-/- mice, Wnt signaling reporters, Lgr5.egfp reporter mice Frontiers in immunology High 28928734
2017 C3aR and C5aR are expressed by human and mouse pancreatic islet β-cells and α-cells. Activation of C3aR (and C5aR1) potentiated glucose-induced insulin secretion, increased intracellular Ca2+ and ATP generation, and protected islets from cytokine/palmitate-induced apoptosis. Glucose-conditioned islet media activated C3aR-driven β-arrestin recruitment. β-arrestin assay (DiscoverX), radioimmunoassay for insulin, Ca2+ imaging, ATP assay, apoptosis assay in human and mouse islets Cellular and molecular life sciences High 28921001
2018 Platelet-expressed C3aR regulates distinct steps of thrombus formation (adhesion, spreading, Ca2+ influx) by mediating activation of the small GTPase Rap1b. Platelet-specific reconstitution experiments (C3aR-/- mice reconstituted with C3aR+/+ platelets) demonstrated that platelet C3aR specifically drives bleeding arrest, in vivo thrombosis, experimental stroke, and myocardial infarction outcomes. Rap1b was identified as a downstream effector by nano-LC-MS/MS. C3aR-/- mice, platelet reconstitution, intravital microscopy, in vitro platelet function assays, nano-LC-MS/MS for Rap1b identification Circulation High 29802205
2018 C3-C3aR signaling activates STAT3 as a direct downstream target mediating tau pathogenesis. Deletion of C3ar1 in PS19 tauopathy mice rescued tau pathology, attenuated disease-associated microglia and neurotoxic astrocyte signatures, and reduced neuroinflammation, synaptic deficits, and neurodegeneration. RNA-seq identified a C3aR-dependent transcription factor network regulating the reactive glial switch. C3ar1-/- in PS19 tauopathy mice, RNA-seq, cell-type-specific transcriptomics, STAT3 signaling analysis Neuron High 30415998
2018 The C3a-C3aR axis in smooth muscle cells promotes thoracic aortic dissection (TAD) by upregulating matrix metalloproteinase 2 (MMP2) expression. C3aR KO inhibited BAPN-induced TAD formation and reduced MMP2 expression. Recombinant C3a stimulation enhanced MMP2 expression and activation in mechanically stretched smooth muscle cells. MMP2-knockdown mice had reduced TAD formation. C3aR KO mice, BAPN-induced TAD model, MMP2 shRNA knockdown via AAV, in vitro C3a stimulation of stretched SMCs Journal of immunology High 29367209
2019 C3aR1 exerts neuroprotection after spinal cord injury by acting as a physiological antagonist of CXCR2-driven neutrophil mobilization from bone marrow. Mechanistically, C3aR1 engages PTEN (a negative regulator of PI3K/AKT) to restrain CXCR2-driven BM neutrophil mobilization following trauma. C3aR1-/- mice with SCI model, PTEN pathway analysis, neutrophil mobilization assays, PI3K/AKT measurements JCI insight High 31045582
2019 VEGFR2 survival and mitotic signaling requires concurrent C3aR1/C5aR1 and IL-6R-gp130 co-signaling. C3aR1/C5aR1 blockade totally abolished VEGFR2 auto-phosphorylation and downstream Src, ERK, AKT, mTOR, and STAT3 activation, and EC cell cycle entry. The four receptors are physically interactive as shown by Co-IP, confocal microscopy, ligand pulldown, and BRET assays. VEGF-A augments C3a/C5a/IL-6 production via p-Tyk2/p-STAT3. Co-immunoprecipitation, confocal microscopy, BRET, ligand pulldown, VEGFR2 phosphorylation assays, murine retinal angiogenesis Journal of cell science High 30765465
2019 T cell-expressed C3aR1 induces CD8+ T cell proliferation, mTOR activation, and T-bet expression during allograft rejection. Host C3aR1 indirectly facilitates alloreactive CD8+ T cell expansion by amplifying APC costimulatory molecule expression and innate cytokine production. Demonstrated by reciprocal adoptive transfers of WT or C3ar1-/- CD8+ T cells. Cardiac allograft model, C3ar1-/- mice, reciprocal adoptive transfers, mTOR/T-bet signaling, flow cytometry American journal of transplantation High 30565852
2019 B2 cell-autonomous autocrine C3aR1/C5aR1 signaling is required for follicular B2 cell activation, CD40 upregulation, IL-6 production, AID/Bcl-6 expression, and class switch recombination. B2 cells produce factor I and C3 and autophosphorylate CD19. C3ar1-/- mice produced only IgM after OVA immunization with no other isotypes. C3ar1-/- mice, OVA immunization, μMT reconstitution with WT/KO B2 cells, CSR analysis, factor I/C3 production assays Journal of immunology High 31217324
2020 TLQP-21 increases motility and phagocytic capacity of murine microglia through C3aR1 signaling. Primary C3aR1-null microglia have impaired basal phagocytic function and do not respond to TLQP-21 or C3a super-agonist. RNA-seq of primary microglia revealed overlapping transcriptomic changes induced by TLQP-21 and C3a super-agonist, linked to cell migration and proliferation pathways. Human TLQP-21 similarly activates human microglia. Phagocytosis/migration assays, RNA-seq of C3aR1-null vs WT primary microglia, intracerebroventricular TLQP-21 in 5xFAD mice Molecular neurodegeneration High 31924226
2020 C3a-C3aR signaling in cancer-associated fibroblasts (CAFs) facilitates breast cancer lung metastasis by augmenting pro-metastatic cytokine secretion and extracellular matrix component expression via PI3K-AKT pathway activation. Ex vivo and in vivo assays, genetic and pharmacological C3aR blockade, PI3K-AKT signaling analysis in CAFs, mouse metastasis models Journal of experimental & clinical cancer research Medium 31931851
2021 Complement activation via the lectin pathway (MBL-dependent, C4-dependent) generates C3a which drives sarcoma progression and immunosuppression through C3aR on tumor-associated macrophages. C3aR deficiency (but not C5aR1 or C5aR2 deficiency) mirrors C3-/- phenotype. C3/C3aR deficiency reduces macrophage accumulation and functional skewing and increases T cell activation and anti-PD-1 response. Transcriptional profiling revealed enrichment of MHC II antigen presentation in C3-deficient macrophages. Systematic genetic KO (C3, MBL1/2, C4, C1q, factor B, C3aR, C5aR1, C5aR2), transplanted sarcoma models, transcriptional profiling of tumor-infiltrating macrophages Nature cancer High 34505065
2021 C3aR signaling on NK cells inhibits their infiltration into the tumor microenvironment by promoting direct physical interaction between C3aR and the integrin LFA-1, driving LFA-1 into a high-affinity conformation that decreases NK cell migration into tumors. C3aR blockade in NK cell tumor models, protein interaction assays (C3aR-LFA-1 co-localization/interaction), LFA-1 conformation assays Cancer immunology research Medium 34819308
2021 The purported C3aR antagonist SB290157 is actually a potent C3aR agonist in transfected cells and acts as a partial agonist at C5aR2 by mediating β-arrestin recruitment, leading to dampening of C5a-induced ERK signaling in primary macrophages. Its apparent antagonism of ligand-stimulated C3aR calcium flux is caused by potent β-arrestin-mediated receptor internalization. β-arrestin recruitment assays, ERK signaling assays in human and mouse primary macrophages, receptor internalization assays Frontiers in pharmacology High 33551801
2022 C3aR signaling in the prefrontal cortex modulates synaptic pruning in depression via STAT3 activation. C3aR blockade inhibited hyperactivation of the microglial APT2/DHHC7 palmitoylation cycle, which mediates STAT3 translocation and proinflammatory cytokine expression, and attenuated excessive synaptic pruning. IL-1R/NF-κB signaling in astrocytes drives C3 release upstream of C3aR. Proteomic analysis, C3aR antagonist treatment in LPS/CUMS mouse models, STAT3/palmitoylation assays, synapse quantification Cell & bioscience Medium 35715851
2022 C3aR signaling contributes to renal interstitial fibrosis by promoting NLRP3 inflammasome activation and assembly in renal tubular epithelial cells. C3aR deficiency in UUO mice attenuated NLRP3 inflammasome activation and fibrosis; NLRP3 inhibition did not affect C3aR expression, placing C3aR upstream of NLRP3. C3aR-/- mice (UUO model), MCC950 NLRP3 inhibitor, Western blot, immunohistochemistry Life sciences Medium 36041502
2022 C3aR incorporating as a costimulatory domain in CAR-T cells (BB-ζ-C3aR) promotes Th17 phenotype expansion, memory T cell induction, and suppresses Tregs, enhancing antitumor efficacy. This demonstrates that C3aR signaling in T cells drives Th17 differentiation. CAR-T cell engineering, in vitro cytotoxicity, ALL/MM xenograft mouse models, T cell phenotyping Journal of hematology & oncology Medium 35597971
2022 C3aR in astrocytes mediates A1 (neurotoxic) astrocyte polarization contributing to chronic post-thoracotomy pain. AAV-mediated C3aR knockdown in astrocytes inhibited LPS-induced A1 polarization, reduced C3/GFAP expression, alleviated mechanical withdrawal threshold, and increased neuroprotective A2 astrocytes. AAV2/9-rC3ar1 shRNA-GFAP in vivo knockdown, RT-PCR, Western blot, co-immunofluorescence, scRNA-seq, behavioral tests Biochimica et biophysica acta. Molecular basis of disease Medium 36871753
2022 CRISPR genome-scale screen identified C3aR as critical for macrophage capture of pathogenic fungi (Histoplasma, Candida, Coccidioides) but dispensable for phagocytosis of bacteria and latex beads. C3aR localizes to the early phagosome during Hc infection and coordinates actin-rich membrane protrusion formation promoting fungal capture. The ER membrane complex (EMC) promotes C3aR surface expression. Genome-scale CRISPR-Cas9 screen, C3aR-/- macrophages, live imaging of phagosome formation, actin dynamics assay PLoS pathogens High 36174103
2023 Cryo-EM/crystal structures of C3a-bound C3aR and apo-C3aR were determined. Mutagenesis analysis revealed a conserved anaphylatoxin recognition pattern distinct from chemokine receptors, unique pocket topology mediating ligand selectivity for C3aR vs. C5aR1, and a common receptor activation mechanism between the two receptors. Cryo-EM structure determination of C3a-C3aR complex and apo-C3aR, mutagenesis, functional signaling assays Nature chemical biology High 37169960
2023 C3aR1 couples preferentially to Gi/o/z proteins and recruits β-arrestins to cause internalization. TLQP-21 exhibits biased signaling toward Gi/o-mediated pathways relative to β-arrestin recruitment compared to C3a63-77. SB290157 acts as a potent C3aR1 agonist whose apparent antagonism of calcium flux is explained by β-arrestin-mediated receptor internalization. Ligand-mediated bias impacts Ca2+ influx, lipolysis in adipocytes, phagocytosis in microglia, and degranulation in mast cells. BRET G protein coupling assays, β-arrestin recruitment assays, internalization assays, adipocyte lipolysis, microglial phagocytosis, mast cell degranulation The Journal of biological chemistry High 38072064
2023 C3aR deletion in microglia rescues dysregulated lipid profiles and improves microglial phagocytic and clustering abilities in Alzheimer's disease. C3ar1-null microglia show lower HIF-1α expression, resistance to hypoxia-mimetic-induced metabolic changes, and reduced lipid droplet accumulation, with improved receptor recycling and Aβ phagocytosis. A heightened C3aR/HIF-1α signaling axis underlies microglial metabolic dysfunction in AD. C3ar1-KI reporter mouse, C3ar1-KO × APP-KI mice, primary microglial cultures, transcriptomic analysis, lipid profiling, phagocytosis assays The Journal of clinical investigation High 37317973
2023 C3aR-initiated signaling is a critical mechanism of podocyte injury in membranous nephropathy. C3aR antagonists and C3AR gene silencing in primary human podocytes (in a glomerulus-on-a-chip model) reduced MN serum-induced oxidative stress and prevented albumin leakage; inhibition of MAC formation did not affect permselectivity. C3aR antagonist prevented proteinuria in a mouse MN model. Glomerulus-on-a-chip with primary human podocytes, C3AR siRNA knockdown, C3aR antagonist, mouse MN model, proteinuria measurement JCI insight High 38227377
2024 In NPM1-mutated AML, C3aR stimulation with C3a activates ERK1/2 and increases AML cell survival. C3AR is specifically expressed on NPM1-mutated AML cells (including leukemic stem cells co-marked by GPR56) but absent from normal hematopoietic stem/progenitor cells. Anti-C3AR antibodies elicit NK cell-mediated killing of AML cells ex vivo. Flow cytometry screen (362 markers), scRNA-seq, C3a stimulation/ERK1/2 assay, antibody-mediated NK cell killing, xenotransplantation Blood advances High 36383712
2024 NFAT1 in tumor-associated macrophages transcriptionally activates C3 expression, increasing C3a secretion which binds C3aR and promotes M2-like macrophage polarization by activating TIM-3. C3a/C3aR also activates the Ca2+-NFAT1 pathway forming a positive feedback loop sustaining M2 polarization and promoting mesenchymal transition of glioma stem cells. Nfat1-/- mouse glioma model, C3aR inhibitor, TIM-3 blocking, Ca2+ signaling assays, transcriptional activity assays Cancer immunology research Medium 38289255
2024 Male adipocyte-specific C3aR1 KO mice exhibit enhanced white adipose tissue thermogenesis and increased respiration, while female adipocyte-specific C3aR1 KO mice display decreased brown fat thermogenesis and cold intolerance, revealing sexual dimorphism in the adipsin/C3a/C3aR1 axis in regulating adaptive thermogenesis. Adipocyte-specific C3aR1 KO mice (male and female), Adipsin-KO mice, metabolic phenotyping, cold tolerance tests JCI insight High 38713526
2024 C3aR modulates susceptibility to LPS-induced depressive-like behaviors through regulation of glutamatergic neuronal excitability in the medial prefrontal cortex. C3aR deletion or antagonism in mPFC confers resilience; re-expression of C3aR in mPFC neurons of KO mice restores susceptibility. C3aR-null mPFC glutamatergic neurons display hyperexcitability upon LPS, which is anti-depressant. C3aR KO mice, intra-mPFC AAV C3aR antagonism/expression, chemogenetic manipulation of mPFCGlu neurons, electrophysiology, behavioral tests Progress in neurobiology High 38641040
2024 C3a promotes neuronal apoptosis and α-synuclein pathology in Parkinson's disease through C3aR-mediated modulation of GSK3β. Complement C3 is released from astrocytes (TLR2/NF-κB dependent), and astrocyte-neuron communication via C3/C3aR influences neuronal apoptosis and α-syn pathology in PD models. α-syn PFF mouse models, C3 overexpression/knockdown, TLR2/NF-κB inhibition in primary astrocytes, GSK3β activity assays Brain, behavior, and immunity Medium 39288893
2024 C3a exacerbates neuroinflammation after subarachnoid hemorrhage via the C3aR-ERK-P2X7-NLRP3 inflammasome signaling axis. C3aR engagement promotes ATP efflux by activating ERK1/2 phosphorylation, which activates P2X7, leading to NLRP3 inflammasome assembly. C3aR interference reduced LDH, IL-1β, caspase-1, NLRP3, ASC oligomerization, and ATP release in BV-2 cells. BV-2 cell heme stimulation model, C3aR siRNA, ERK inhibitor, P2X7 antagonist (JNJ-55308942), in vivo SB290157 in SAH mice Inflammation Medium 39528767

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2018 Complement C3aR Inactivation Attenuates Tau Pathology and Reverses an Immune Network Deregulated in Tauopathy Models and Alzheimer's Disease. Neuron 390 30415998
2012 Absence of signaling into CD4⁺ cells via C3aR and C5aR enables autoinductive TGF-β1 signaling and induction of Foxp3⁺ regulatory T cells. Nature immunology 255 23263555
2016 Coagulation induced by C3aR-dependent NETosis drives protumorigenic neutrophils during small intestinal tumorigenesis. Nature communications 215 26996437
2020 Microglia exacerbate white matter injury via complement C3/C3aR pathway after hypoperfusion. Theranostics 167 31903107
2003 Mobilization studies in mice deficient in either C3 or C3a receptor (C3aR) reveal a novel role for complement in retention of hematopoietic stem/progenitor cells in bone marrow. Blood 147 14604969
2007 Local production and activation of complement up-regulates the allostimulatory function of dendritic cells through C3a-C3aR interaction. Blood 142 18056835
1996 Expression cloning of the human C3a anaphylatoxin receptor (C3aR) from differentiated U-937 cells. European journal of immunology 129 8765043
2020 The complement C3-C3aR pathway mediates microglia-astrocyte interaction following status epilepticus. Glia 119 33314324
2012 C5aR and C3aR antagonists each inhibit diet-induced obesity, metabolic dysfunction, and adipocyte and macrophage signaling. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 118 23118029
2023 Helicobacter pylori-derived outer membrane vesicles contribute to Alzheimer's disease pathogenesis via C3-C3aR signalling. Journal of extracellular vesicles 110 36792546
2018 Functional Relevance of the Anaphylatoxin Receptor C3aR for Platelet Function and Arterial Thrombus Formation Marks an Intersection Point Between Innate Immunity and Thrombosis. Circulation 92 29802205
2013 Identification of the C3a receptor (C3AR1) as the target of the VGF-derived peptide TLQP-21 in rodent cells. The Journal of biological chemistry 81 23940034
2020 VGF-derived peptide TLQP-21 modulates microglial function through C3aR1 signaling pathways and reduces neuropathology in 5xFAD mice. Molecular neurodegeneration 74 31924226
2017 Monitoring C3aR Expression Using a Floxed tdTomato-C3aR Reporter Knock-in Mouse. Journal of immunology (Baltimore, Md. : 1950) 72 28626064
2016 Contribution of the anaphylatoxin receptors, C3aR and C5aR, to the pathogenesis of pulmonary fibrosis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 71 26956419
2019 Complement receptor C3aR1 controls neutrophil mobilization following spinal cord injury through physiological antagonism of CXCR2. JCI insight 70 31045582
2019 The Complement Receptors C3aR and C5aR Are a New Class of Immune Checkpoint Receptor in Cancer Immunotherapy. Frontiers in immunology 70 31379815
2009 Defective engraftment of C3aR-/- hematopoietic stem progenitor cells shows a novel role of the C3a-C3aR axis in bone marrow homing. Leukemia 61 19357704
2021 Complement activation promoted by the lectin pathway mediates C3aR-dependent sarcoma progression and immunosuppression. Nature cancer 59 34505065
2022 IL-1R/C3aR signaling regulates synaptic pruning in the prefrontal cortex of depression. Cell & bioscience 57 35715851
2008 Role of complement anaphylatoxin receptors (C3aR, C5aR) in the development of the rat cerebellum. Molecular immunology 55 18635264
2020 C3a-C3aR signaling promotes breast cancer lung metastasis via modulating carcinoma associated fibroblasts. Journal of experimental & clinical cancer research : CR 54 31931851
2023 Complement C3aR depletion reverses HIF-1α-induced metabolic impairment and enhances microglial response to Aβ pathology. The Journal of clinical investigation 53 37317973
2014 The TLQP-21 peptide activates the G-protein-coupled receptor C3aR1 via a folding-upon-binding mechanism. Structure (London, England : 1993) 50 25456411
2005 Expression of the anaphylatoxin receptors C3aR and C5aR is increased in fatal asthma. The Journal of allergy and clinical immunology 50 15940127
2023 Revealing the signaling of complement receptors C3aR and C5aR1 by anaphylatoxins. Nature chemical biology 49 37169960
2018 The Complement C3a-C3aR Axis Promotes Development of Thoracic Aortic Dissection via Regulation of MMP2 Expression. Journal of immunology (Baltimore, Md. : 1950) 44 29367209
1999 Ligand-induced phosphorylation of anaphylatoxin receptors C3aR and C5aR is mediated by "G protein-coupled receptor kinases. European journal of immunology 42 10508278
2021 Pan-Cancer Analysis of Immune Complement Signature C3/C5/C3AR1/C5AR1 in Association with Tumor Immune Evasion and Therapy Resistance. Cancers 39 34439277
2009 C3aR inhibition reduces neurodegeneration in experimental lupus. Lupus 39 19900981
2017 C3aR and C5aR1 act as key regulators of human and mouse β-cell function. Cellular and molecular life sciences : CMLS 37 28921001
2016 The neuropeptide TLQP-21 opposes obesity via C3aR1-mediated enhancement of adrenergic-induced lipolysis. Molecular metabolism 36 28123945
2023 Cntnap4 partial deficiency exacerbates α-synuclein pathology through astrocyte-microglia C3-C3aR pathway. Cell death & disease 35 37087484
2015 Complement anaphylatoxin receptors C3aR and C5aR are required in the pathogenesis of experimental autoimmune uveitis. Journal of leukocyte biology 33 26394814
2014 The receptor for the complement C3a anaphylatoxin (C3aR) provides host protection against Listeria monocytogenes-induced apoptosis. Journal of immunology (Baltimore, Md. : 1950) 33 24981453
2019 Endothelial progenitor cell transplantation alleviated ischemic brain injury via inhibiting C3/C3aR pathway in mice. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 31 31865842
2021 The "C3aR Antagonist" SB290157 is a Partial C5aR2 Agonist. Frontiers in pharmacology 28 33551801
2020 Protective Role of C3aR (C3a Anaphylatoxin Receptor) Against Atherosclerosis in Atherosclerosis-Prone Mice. Arteriosclerosis, thrombosis, and vascular biology 28 32762445
2021 C3/C3aR inhibition alleviates GMH-IVH-induced hydrocephalus by preventing microglia-astrocyte interactions in neonatal rats. Neuropharmacology 27 34921829
2019 Absence of recipient C3aR1 signaling limits expansion and differentiation of alloreactive CD8+ T cell immunity and prolongs murine cardiac allograft survival. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 27 30565852
2017 C3a Enhances the Formation of Intestinal Organoids through C3aR1. Frontiers in immunology 27 28928734
2019 Follicular B2 Cell Activation and Class Switch Recombination Depend on Autocrine C3ar1/C5ar1 Signaling in B2 Cells. Journal of immunology (Baltimore, Md. : 1950) 25 31217324
2018 Anaphylatoxin Receptors C3aR and C5aR1 Are Important Factors That Influence the Impact of Ethanol on the Adipose Secretome. Frontiers in immunology 25 30294325
2013 The complement anaphylatoxin C3a receptor (C3aR) contributes to the inflammatory response in dextran sulfate sodium (DSS)-induced colitis in mice. PloS one 25 23638016
2019 Distinct roles of the anaphylatoxin receptors C3aR, C5aR1 and C5aR2 in experimental meningococcal infections. Virulence 24 31274379
2024 An NFAT1-C3a-C3aR Positive Feedback Loop in Tumor-Associated Macrophages Promotes a Glioma Stem Cell Malignant Phenotype. Cancer immunology research 23 38289255
2021 Complement C3 and C3aR mediate different aspects of emotional behaviours; relevance to risk for psychiatric disorder. Brain, behavior, and immunity 23 34543680
2024 Transcriptome Analysis Reveals Dynamic Microglial-Induced A1 Astrocyte Reactivity via C3/C3aR/NF-κB Signaling After Ischemic Stroke. Molecular neurobiology 22 38713438
2023 Microglia refine developing retinal astrocytic and vascular networks through the complement C3/C3aR axis. Development (Cambridge, England) 22 36762625
2021 C3aR Signaling Inhibits NK-cell Infiltration into the Tumor Microenvironment in Mouse Models. Cancer immunology research 22 34819308
2020 Aristolochic acid I promotes the invasion and migration of hepatocellular carcinoma cells by activating the C3a/C3aR complement system. Toxicology letters 21 32898628
2024 Astrocyte-neuron communication through the complement C3-C3aR pathway in Parkinson's disease. Brain, behavior, and immunity 20 39288893
2022 Astrocyte-microglia interaction through C3/C3aR pathway modulates neuropathic pain in rats model of chronic constriction injury. Molecular pain 20 36341694
2019 Aristolochic acid I aggravates renal injury by activating the C3a/C3aR complement system. Toxicology letters 20 31048001
2022 C3aR costimulation enhances the antitumor efficacy of CAR-T cell therapy through Th17 expansion and memory T cell induction. Journal of hematology & oncology 19 35597971
2022 Gypenoside XVII, an Active Ingredient from Gynostemma Pentaphyllum, Inhibits C3aR-Associated Synaptic Pruning in Stressed Mice. Nutrients 19 35745148
2019 VEGFR2 survival and mitotic signaling depends on joint activation of associated C3ar1/C5ar1 and IL-6R-gp130. Journal of cell science 19 30765465
2021 Identification and Validation of CYBB, CD86, and C3AR1 as the Key Genes Related to Macrophage Infiltration of Gastric Cancer. Frontiers in molecular biosciences 18 34950700
2023 Functional profiling of the G protein-coupled receptor C3aR1 reveals ligand-mediated biased agonism. The Journal of biological chemistry 16 38072064
2022 Complement C3a Enhances the Phagocytic Activity of B Cells Through C3aR in a Fish. Frontiers in immunology 16 35386704
2022 The complement C3a-C3aR and C5a-C5aR pathways promote viability and inflammation of human retinal pigment epithelium cells by targeting NF-κB signaling. Experimental and therapeutic medicine 16 35837068
2023 Echinacea purpurea (L.) Moench extract suppresses inflammation by inhibition of C3a/C3aR signaling pathway in TNBS-induced ulcerative colitis rats. Journal of ethnopharmacology 15 36754188
2023 C3aR in astrocytes mediates post-thoracotomy pain by inducing A1 astrocytes in male rats. Biochimica et biophysica acta. Molecular basis of disease 15 36871753
2023 Complement Activation and Up-Regulated Expression of Anaphylatoxin C3a/C3aR in Glioblastoma: Deciphering the Links with TGF-β and VEGF. Cancers 15 37174113
2020 Down-Regulation of C3aR/C5aR Inhibits Cell Proliferation and EMT in Hepatocellular Carcinoma. Technology in cancer research & treatment 15 33176600
2024 C3aR-initiated signaling is a critical mechanism of podocyte injury in membranous nephropathy. JCI insight 14 38227377
2024 Adipsin and adipocyte-derived C3aR1 regulate thermogenic fat in a sex-dependent fashion. JCI insight 14 38713526
2022 C3aR contributes to unilateral ureteral obstruction-induced renal interstitial fibrosis via the activation of the NLRP3 inflammasome. Life sciences 14 36041502
2021 Dissociable effects of complement C3 and C3aR on survival and morphology of adult born hippocampal neurons, pattern separation, and cognitive flexibility in male mice. Brain, behavior, and immunity 14 34403734
2012 Participation of complement 3a receptor (C3aR) in the sensitization phase of Th2 mediated allergic contact dermatitis. Experimental dermatology 14 22151392
2022 C-reactive protein inhibits C3a/C3aR-dependent podocyte autophagy in favor of diabetic kidney disease. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 13 35503088
2019 C3aR signaling and gliosis in response to neurodevelopmental damage in the cerebellum. Journal of neuroinflammation 13 31272467
2018 Expression of complement C3, C5, C3aR and C5aR1 genes in resting and activated CD4+ T cells. Immunobiology 13 30612786
2014 Downregulation of complement C3 and C3aR expression in subcutaneous adipose tissue in obese women. PloS one 13 24743347
2012 Decreased expression of complement 3a receptor (C3aR) in human placentas from severe preeclamptic pregnancies. European journal of obstetrics, gynecology, and reproductive biology 13 22901903
2022 C3aR plays both sides in regulating resistance to bacterial infections. PLoS pathogens 12 35925892
2025 C3/C3aR Bridges Spinal Astrocyte-Microglia Crosstalk and Accelerates Neuroinflammation in Morphine-Tolerant Rats. CNS neuroscience & therapeutics 11 39801259
2023 Complement Receptor C3aR1 Contributes to Paclitaxel-Induced Peripheral Neuropathic Pain in Mice and Rats. Journal of immunology (Baltimore, Md. : 1950) 11 37861348
2022 Complement C3a Receptor (C3aR) Mediates Vascular Dysfunction, Hippocampal Pathology, and Cognitive Impairment in a Mouse Model of VCID. Translational stroke research 11 35258803
2021 C3AR1 mRNA as a Potential Therapeutic Target Associates With Clinical Outcomes and Tumor Microenvironment in Osteosarcoma. Frontiers in medicine 11 33748161
2019 RTK signaling requires C3ar1/C5ar1 and IL-6R joint signaling to repress dominant PTEN, SOCS1/3 and PHLPP restraint. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 11 31908021
2018 The C3aR promotes macrophage infiltration and regulates ANCA production but does not affect glomerular injury in experimental anti-myeloperoxidase glomerulonephritis. PloS one 11 29315316
2017 Resveratrol Attenuates Adriamycin-Induced Focal Segmental Glomerulosclerosis through C3aR/C5aR- Sphingosine Kinase 1 Pathway. Pharmacology 11 28797008
2007 Discovery of new C3aR ligands. Part 2: amino-piperidine derivatives. Bioorganic & medicinal chemistry letters 11 17459702
2024 Complement C3aR signaling: Immune and metabolic modulation and its impact on Alzheimer's disease. European journal of immunology 10 38778507
2024 Complement 3a induces the synapse loss via C3aR in mitochondria-dependent NLRP3 activating mechanisms during the development and progression of Alzheimer's disease. Neuroscience and biobehavioral reviews 10 39218048
2024 Complement Molecule C3a Exacerbates Early Brain Injury After Subarachnoid Hemorrhage by Inducing Neuroinflammation Through the C3aR-ERK-P2X7-NLRP3 Inflammasome Signaling Axis. Inflammation 10 39528767
2022 Genome-scale CRISPR screening reveals that C3aR signaling is critical for rapid capture of fungi by macrophages. PLoS pathogens 10 36174103
2020 Blockade of C3a/C3aR axis alleviates severe acute pancreatitis-induced intestinal barrier injury. American journal of translational research 10 33194030
2025 CD81+ senescent-like fibroblasts exaggerate inflammation and activate neutrophils via C3/C3aR1 axis in periodontitis. eLife 9 40801798
2023 C3a/C3aR synergies with TGF-β to promote epithelial-mesenchymal transition of renal tubular epithelial cells via the activation of the NLRP3 inflammasome. Journal of translational medicine 9 38082306
2017 Complement component C3aR constitutes a novel regulator for chick eye morphogenesis. Developmental biology 9 28576690
2024 C3aR in the medial prefrontal cortex modulates the susceptibility to LPS-induced depressive-like behaviors through glutamatergic neuronal excitability. Progress in neurobiology 8 38641040
2024 Microglia aggravate white matter injury via C3/C3aR pathway after experimental subarachnoid hemorrhage. Experimental neurology 8 38866102
2023 The complement receptor C3AR constitutes a novel therapeutic target in NPM1-mutated AML. Blood advances 8 36383712
2022 Molecular signatures of intrarenal complement receptors C3AR1 and C5AR1 correlate with renal outcome in human lupus nephritis. Lupus science & medicine 8 36521939
2021 Autoantibodies against C5aR1, C3aR1, CXCR3, and CXCR4 are decreased in primary Sjogren's syndrome. Molecular immunology 8 33446393
2016 Whole-exome sequencing of a patient with severe and complex hemostatic abnormalities reveals a possible contributing frameshift mutation in C3AR1. Cold Spring Harbor molecular case studies 8 27551680
2000 A novel computational method for predicting the transmembrane structure of G-protein coupled receptors: application to human C5aR and C3aR. Receptors & channels 8 10952089
1999 Ligand binding sites on guinea pig C3aR: point and deletion mutations in the large extracellular loop and vicinity. Biochemical and biophysical research communications 7 10491297