Affinage

C3AR1

C3a anaphylatoxin chemotactic receptor · UniProt Q16581

Length
482 aa
Mass
53.9 kDa
Annotated
2026-06-09
100 papers in source corpus 46 papers cited in narrative 47 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 11/11 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

C3AR1 encodes a seven-transmembrane G protein-coupled receptor with an unusually large second extracellular loop (~175 residues) that binds the complement anaphylatoxin C3a to trigger intracellular signaling (PMID:8765043). The receptor preferentially couples to Gi/o/z proteins and recruits β-arrestins to drive internalization, with ligand identity tuning the balance between G protein signaling and β-arrestin recruitment; the VGF-derived neuropeptide TLQP-21 is a biased agonist favoring Gi/o-mediated signaling over arrestin engagement (PMID:38072064, PMID:23940034). Upon agonist binding, C3aR is rapidly phosphorylated on serine/threonine residues by GRK2/3/5/6, initiating desensitization and internalization (PMID:10508278). Cryo-EM structures of C3a-bound and apo-C3aR define a unique pocket topology that confers anaphylatoxin selectivity distinct from chemokine receptors and reveal an activation mechanism shared with C5aR1 (PMID:37169960). Downstream, C3aR signals through PI3Kγ/Akt/mTOR, ERK, calcium mobilization, and STAT3 to produce strongly context-dependent outputs across many cell types (PMID:23263555, PMID:38072064, PMID:30415998). In hematopoiesis it retains stem/progenitor cells in bone marrow and promotes engraftment via MMP-9 secretion and stromal adhesion (PMID:14604969, PMID:19357704), and it restrains CXCR2-driven neutrophil mobilization through a PTEN/PI3K-AKT axis (PMID:31045582). In adaptive immunity, loss of C3aR signaling drives Foxp3+ regulatory T cell differentiation by suppressing PI3Kγ/Akt/mTOR and engaging autocrine TGF-β1 (PMID:23263555), while autocrine C3aR signaling in B cells is required for class switch recombination (PMID:31217324) and recipient C3aR amplifies alloreactive CD8+ T cell expansion (PMID:30565852). In platelets C3aR activates Rap1b to promote thrombus formation (PMID:29802205), and in adipocytes it potentiates β-adrenergic lipolysis via a Ca2+/ERK/HSL axis with sexually dimorphic effects on adipose thermogenesis (PMID:28123945, PMID:38713526). In the nervous system C3aR is expressed predominantly on microglia (PMID:28626064) and governs microglial metabolic homeostasis and Aβ phagocytosis through a HIF-1α axis (PMID:37317973), tau pathology via STAT3 (PMID:30415998), and neuronal excitability and emotional behavior (PMID:38641040). Across cancer and fibrotic disease the receptor recurrently drives ERK→NLRP3 inflammasome and PI3K-AKT programs and macrophage immunosuppression (PMID:38082306, PMID:31931851, PMID:34505065), and on podocytes it mediates complement-driven albumin permselectivity loss in membranous nephropathy independent of the membrane attack complex (PMID:38227377). C3aR also functions within a physically interactive VEGFR2–C3aR1–C5aR1–IL-6R signaling platform required for receptor tyrosine kinase growth signaling (PMID:30765465).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 1996 High

    Established the molecular identity of the C3a receptor as a functional GPCR, answering whether C3a signals through a defined seven-transmembrane receptor.

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

    PMID:8765043

    Open questions at the time
    • G protein coupling shown only with co-transfected Gα-16, not native G proteins
    • Function of the large second extracellular loop undefined
  2. 1999 High

    Defined how agonist-bound C3aR is desensitized, identifying GRK-mediated serine/threonine phosphorylation as the regulatory mechanism.

    Evidence Phosphorylation/radiolabeling assays with GRK2/3/5/6 overexpression and antibody inhibition in COS-7 and primary mast cells

    PMID:10508278

    Open questions at the time
    • Specific phosphoacceptor residues not mapped
    • Link to β-arrestin recruitment not directly established here
  3. 2003 High

    Demonstrated a physiological role in hematopoiesis, showing C3aR retains stem/progenitor cells in bone marrow by enhancing SDF-1 responsiveness.

    Evidence C3aR-/- and C3-/- mouse mobilization studies with bone marrow chimeras and SB290157 antagonist

    PMID:14604969

    Open questions at the time
    • Molecular link between C3aR and SDF-1/CXCR4 responsiveness undefined
    • SB290157 later shown to have agonist activity
  4. 2009 High

    Resolved the engraftment mechanism distinct from mobilization, attributing it to C3aR-driven MMP-9 secretion and stromal adhesion.

    Evidence C3aR-/- HSPC transplantation, CFU assays, MMP-9/adhesion assays, human cord blood NOD/SCID xenografts

    PMID:19357704

    Open questions at the time
    • Signaling pathway from C3aR to MMP-9 induction not mapped
    • C3a-enhanced SDF-1 response found C3aR-independent, complicating the model
  5. 2013 High

    Identified a second, non-complement ligand class by showing the VGF peptide TLQP-21 is a C3aR1 agonist, broadening receptor pharmacology.

    Evidence Transcriptome screen of CHO-K1 cells with antagonist pharmacology, siRNA, pertussis toxin sensitivity, and macrophage migration

    PMID:23940034

    Open questions at the time
    • Demonstrated for rodent receptor; human potency lower
    • Whether TLQP-21 and C3a share the same binding pocket not addressed
  6. 2014 High

    Defined the structural basis of TLQP-21 binding, showing a disorder-to-order transition and a C-terminal hot spot governing activity.

    Evidence NMR/structural analysis with systematic TLQP-21 mutagenesis and cell-based functional assays

    PMID:25456411

    Open questions at the time
    • Receptor-side contacts not yet resolved at this stage
    • Human variant has reduced potency
  7. 2012 High

    Established C3aR as a brake on regulatory T cell induction, linking its signaling to PI3Kγ/Akt/mTOR suppression and autocrine TGF-β1.

    Evidence C3aR/C5aR-deficient mice, pharmacological antagonism, signaling dissection, Foxp3 reporters, human iTreg induction

    PMID:23263555

    Open questions at the time
    • Relative contributions of C3aR vs C5aR not fully separated
    • Mechanism of C3a production in T cell microenvironment incomplete
  8. 2014 High

    Extended C3aR function to cell survival, showing it protects immune cells against Listeria-induced apoptosis via Bcl-2/Fas/caspase-3 control.

    Evidence C3aR-/- mouse infection model with TUNEL, caspase-3 activity, and Bcl-2/Fas expression

    PMID:24981453

    Open questions at the time
    • Direct signaling pathway from C3aR to apoptotic machinery not mapped
  9. 2018 High

    Defined a platelet-specific effector, identifying Rap1b activation as the mechanism by which C3aR promotes thrombosis.

    Evidence C3aR-/- mice with platelet reconstitution, intravital microscopy, nano-LC-MS/MS identification of Rap1b, stroke/MI models

    PMID:29802205

    Open questions at the time
    • Coupling between C3aR and Rap1b activation not biochemically reconstituted
  10. 2016 High

    Revealed a metabolic role, showing C3aR1 potentiates β-adrenergic lipolysis through Ca2+/ERK/HSL rather than acting as an intrinsic lipolytic signal.

    Evidence C3aR1-KO and β-AR-deficient mice, 3T3-L1/primary adipocyte assays, in vivo obesity experiments

    PMID:28123945

    Open questions at the time
    • Molecular point of crosstalk with β-adrenergic receptor unresolved
  11. 2017 High

    Mapped the cellular expression landscape of C3aR1, establishing microglia, macrophages, and adipose as principal sites and excluding circulating lymphoid cells.

    Evidence tdTomato-C3aR reporter knock-in mouse with flow cytometry and immunohistochemistry across tissues

    PMID:28626064

    Open questions at the time
    • Reporter expression in mouse may not fully reflect human distribution
    • Inducible expression under disease conditions not captured
  12. 2019 High

    Placed C3aR1 within a physical RTK co-signaling platform required for VEGFR2-driven endothelial growth signaling.

    Evidence Co-IP, BRET, confocal, ligand pulldown, C3aR1/C5aR1 blockade, and in vivo retinal angiogenesis

    PMID:30765465

    Open questions at the time
    • Stoichiometry and architecture of the four-receptor complex undefined
    • Whether the platform forms in non-endothelial cells unknown
  13. 2019 High

    Established cell-intrinsic and autocrine roles in adaptive immunity, showing C3aR1 is required for B cell class switch recombination and amplifies alloreactive CD8+ T cell responses.

    Evidence C3ar1-/- mice with reciprocal adoptive transfer into μMT and C3-/- recipients; cardiac allograft and CD8 expansion analysis with mTOR/T-bet readouts

    PMID:30565852 PMID:31217324

    Open questions at the time
    • Source and regulation of autocrine C3a/C3 in lymphocytes incompletely defined
  14. 2018 High

    Showed C3aR drives tissue remodeling and fibrotic disease via MMP and inflammasome effectors in vascular and renal pathology.

    Evidence C3aR-/- mice and effector knockdown in BAPN aortic dissection (MMP2) and UUO renal fibrosis (NLRP3) models

    PMID:29367209 PMID:36041502 PMID:38082306

    Open questions at the time
    • Multiple effector pathways (MMP2, ERK→NLRP3) not unified into a single mechanism
    • Some renal findings are single-lab Medium confidence
  15. 2018 High

    Established C3aR as a central driver of neuroinflammatory and neurodegenerative pathology, identifying STAT3 and HIF-1α as key microglial effectors.

    Evidence C3ar1-/- crosses with PS19 tauopathy and APP-KI mice, RNA-seq, primary microglia metabolic/phagocytosis assays, and multiple injury models

    PMID:30415998 PMID:31903107 PMID:33314324 PMID:37317973

    Open questions at the time
    • Ligand(s) driving CNS C3aR signaling in some contexts unconfirmed
    • How STAT3 and HIF-1α arms relate mechanistically unclear
  16. 2021 High

    Demonstrated a tumor-immunosuppressive role, showing C3aR shapes macrophage polarization, antigen presentation, and checkpoint therapy responsiveness.

    Evidence Systematic complement KO comparison in sarcoma with macrophage transcriptional profiling and anti-PD-1 combination; tumor models in breast cancer and glioma

    PMID:31931851 PMID:34505065 PMID:38289255

    Open questions at the time
    • Generalizability of the lectin-pathway→C3aR axis across tumor types untested
    • Some downstream loops (NFAT1, TIM-3) are single-lab Medium confidence
  17. 2021 High

    Exposed the off-target pharmacology of the widely used compound SB290157, reframing it as a context-dependent C3aR agonist and partial C5aR2 agonist.

    Evidence β-arrestin and ERK assays across C3aR/C5aR1/C5aR2 transfected cells and primary human/mouse macrophages

    PMID:33551801

    Open questions at the time
    • Reinterpretation of prior SB290157 studies needed
    • Determinants of cell-context switch between agonism and antagonism unresolved
  18. 2023 High

    Provided the definitive structural and signaling framework, resolving the C3a-bound receptor and systematically characterizing Gi/o/z coupling and β-arrestin bias.

    Evidence Cryo-EM/crystallography of C3a-C3aR and apo-C3aR with mutagenesis; BRET G protein and β-arrestin assays with functional readouts in adipocytes, microglia, and mast cells

    PMID:37169960 PMID:38072064

    Open questions at the time
    • Structure of TLQP-21-bound receptor not determined
    • Structural basis of biased agonism not directly visualized
  19. 2024 High

    Refined disease relevance by isolating podocyte C3aR as the critical complement effector in membranous nephropathy and revealing sex-dependent adipose function.

    Evidence Glomerulus-on-a-chip with siRNA/antagonist and in vivo MN model; adipocyte-specific C3aR1-KO in both sexes with metabolic phenotyping

    PMID:38227377 PMID:38713526

    Open questions at the time
    • Molecular basis of sexual dimorphism in adipose C3aR signaling incomplete
    • Podocyte oxidative-stress mechanism downstream of C3aR not fully mapped
  20. 2023 High

    Identified a non-immune-classical role in innate immunity, showing C3aR1 enables macrophage capture of fungal pathogens via phagosomal localization and actin protrusions.

    Evidence Genome-scale CRISPR screen with C3aR KO validation, phagocytosis assays across fungi/bacteria/beads, phagosomal imaging, and EMC epistasis

    PMID:36174103

    Open questions at the time
    • Whether a defined ligand drives this capture function unknown
    • Selectivity for fungi over bacteria mechanistically unexplained

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single receptor with one structural framework produces such divergent, cell-type-specific outputs—and the identity of the non-C3a ligand(s) implicated in CNS and behavioral phenotypes—remains unresolved.
  • Alternative ligand driving C3a-independent anxiety phenotype unidentified
  • No unifying model linking Gi/o vs β-arrestin bias to specific tissue outcomes
  • Structural basis of biased agonism by TLQP-21 vs C3a not determined

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 GO:0001618 virus receptor activity 1
Localization
GO:0005886 plasma membrane 3 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-168256 Immune System 4 R-HSA-162582 Signal Transduction 3 R-HSA-8953897 Cellular responses to stimuli 3
Partners
C3AGRK2GRK3GRK5GRK6LFA-1TLQP-21VEGFR2
Complex memberships
VEGFR2–C3aR1–C5aR1–IL-6R signaling platform

Evidence

Reading pass · 47 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 Human C3aR was cloned from differentiated U-937 cells; it encodes a 482-residue GPCR with seven transmembrane helices and an unusually large second extracellular loop (~175 residues). Transfected HEK-293 cells specifically bound iodinated C3a, and CHO cells co-transfected with C3aR and Gα-16 showed increased phosphoinositide hydrolysis in response to C3a, demonstrating functional G protein coupling. Expression cloning, radioligand binding assay, phosphoinositide hydrolysis assay in transfected cells European journal of immunology High 8765043
1999 Agonist-stimulated C3aR undergoes rapid (t½ ~15 s), dose-dependent, reversible phosphorylation on serine and threonine residues (not tyrosine), mediated by GRK2, GRK3, GRK5, and GRK6. Overexpression of each GRK enhanced C3a-induced C3aR phosphorylation 1.5–1.9-fold, while antibody-mediated inhibition of endogenous GRK2/3 blocked phosphorylation. The same phosphorylation was detected on endogenously expressed C3aR in HMC-1 mast cells. Metabolic radiolabeling/phosphorylation assay, GRK overexpression in COS-7 cells, antibody-mediated GRK inhibition, phosphoamino acid analysis European journal of immunology High 10508278
2003 The C3a–C3aR axis retains hematopoietic stem/progenitor cells (HSPCs) in bone marrow by increasing their responsiveness to SDF-1. C3aR-/- mice and C3-/- mice showed significantly enhanced G-CSF-induced HSPC mobilization. Chimeric mouse experiments demonstrated that C3aR deficiency on graft-derived (hematopoietic) cells—not host stromal cells—was responsible for the increased mobilization. C3aR-/- and C3-/- mouse mobilization studies, bone marrow chimeras, G-CSF treatment, C3aR antagonist SB290157 Blood High 14604969
2007 C3aR signaling on dendritic cells (DCs) upregulates surface MHC and costimulatory molecule expression and is required for efficient T-cell priming against alloantigen. DCs lacking C3aR or treated with C3aR antagonist showed defective allostimulation and impaired skin allograft rejection. The alternative complement pathway (factor B-dependent, C4-independent) was identified as the relevant source of C3a. C3aR-/- bone marrow-derived DC allostimulation assays, skin allograft model, complement-deficient DC experiments (factor B-/-, C4-/-) Blood High 18056835
2008 C3aR agonist treatment in neonatal rat cerebellum decreased the thickness of the external granule cell layer (EGL) and increased the internal granule cell layer (IGL), consistent with accelerated granule cell migration. Video-microscopy of cultured granule neurons confirmed a direct role for C3aR in cell motility. In vivo sub-dural injection of C3aR agonist/antagonist, histological analysis of cerebellar cortical layers, live video-microscopy of cultured neurons Molecular immunology Medium 18635264
2009 C3aR on hematopoietic stem/progenitor cells promotes engraftment by augmenting MMP-9 secretion and cell adhesion to stroma. C3aR-/- HSPCs transplanted into lethally irradiated recipients showed 5–7 day delayed platelet/leukocyte recovery and reduced CFU-spleen. Blockade of C3aR on human cord blood CD34+ cells with SB290157 also impaired engraftment in NOD/SCID mice. Although C3a-enhanced SDF-1 responsiveness persisted in C3aR-/- cells (C3aR-independent effect), C3aR-/- cells secreted less MMP-9 and showed impaired stromal adhesion. C3aR-/- HSPC transplantation into irradiated mice, CFU assays, MMP-9 secretion assay, adhesion assay, human cord blood NOD/SCID xenograft with C3aR antagonist Leukemia High 19357704
2012 Absence of C3aR (and C5aR) signaling in CD4+ T cells leads to cessation of PI3Kγ/Akt/mTOR signaling, increased PKA activity, initiation of autoinductive TGF-β1 signaling, and differentiation into Foxp3+ induced regulatory T cells. Endogenous TGF-β1 suppressed C3aR/C5aR signaling by preventing C3a/C5a production and upregulating C5L2. The resulting iTreg cells showed enhanced stability and suppressed autoimmune disease. C3aR/C5aR-deficient mice, pharmacological antagonism, signaling pathway analysis (PI3Kγ, Akt, mTOR, PKA), Foxp3 reporter assays, autoimmune disease models, human iTreg induction Nature immunology High 23263555
2013 The VGF-derived neuropeptide TLQP-21 acts as a ligand for rodent C3AR1. Unbiased transcriptome sequencing of responsive CHO-K1 cells combined with defined receptor antagonists and siRNA knockdown identified C3AR1 as the GPCR mediating TLQP-21 signaling. TLQP-21 activity was pertussis toxin-sensitive (consistent with Gi coupling of C3AR1) and the peptide directed migration of mouse RAW264.7 macrophages through C3aR1. Transcriptome sequencing, receptor antagonist pharmacology, siRNA knockdown, pertussis toxin sensitivity assay, cell migration assay The Journal of biological chemistry High 23940034
2014 TLQP-21 is intrinsically disordered and adopts an α-helical conformation (disorder-to-order transition) upon binding cells expressing C3aR1. The C-terminus of TLQP-21 constitutes the functional hot spot: mutations in the last four amino acids progressively reduce bioactivity, and a single R21A mutation or C-terminal amidation abolishes function completely. Human TLQP-21 (S20A variant) activates human C3aR1 with lower potency than the rodent sequence. NMR/structural biology of TLQP-21, site-directed mutagenesis of TLQP-21, cell-based functional assays Structure (London, England : 1993) High 25456411
2014 C3aR signaling protects myeloid and lymphoid cells against Listeria monocytogenes-induced apoptosis. C3aR-/- mice showed increased bacterial burden and mortality, with increased Fas expression, higher caspase-3 activity, and reduced Bcl-2 expression in splenocytes, without defects in macrophage function or cytokine/chemokine responses. C3aR-/- mouse infection model, TUNEL staining, caspase-3 activity assay, Bcl-2/Fas expression, bacterial burden measurement Journal of immunology High 24981453
2016 C3aR on neutrophils drives NETosis following LPS-induced complement C3a upregulation, which induces coagulation and N2 pro-tumorigenic polarization in intestinal tumorigenesis. Mouse model of spontaneous intestinal tumorigenesis, C3aR expression analysis on neutrophils, NET formation assay, coagulation assays Nature communications Medium 26996437
2016 TLQP-21 opposes obesity via C3aR1-mediated enhancement of adrenergic-induced lipolysis. TLQP-21 does not possess intrinsic lipolytic activity but potentiates β-adrenergic receptor-induced lipolysis through a mechanism requiring Ca2+ mobilization and ERK activation of hormone-sensitive lipase (HSL). Chronic peripheral TLQP-21 treatment decreased body weight/fat mass in diet-induced obese mice in a β-adrenergic and C3aR1-dependent manner. C3aR1 KO mice, β-AR-deficient mice, 3T3-L1 and primary adipocyte in vitro assays, in vivo lipolysis experiments, pharmacological approaches Molecular metabolism High 28123945
2017 C3aR1 is strongly expressed in the brain (predominantly on microglia), lung, intestinal lamina propria, and visceral adipose tissue; most macrophage and eosinophil populations are C3aR-positive. Notably, bone marrow neutrophils, mast cells, and all circulating lymphoid cells were C3aR-negative in mice, as determined by a reporter knock-in mouse. Floxed tdTomato-C3aR reporter knock-in mouse, flow cytometry, immunohistochemistry across multiple tissues Journal of immunology High 28626064
2017 C3aR1 activation by C3a promotes intestinal stem cell expansion and organoid formation via Wnt-signaling. C3-/- and C3aR1-/- mice showed significantly limited intestinal organoid formation; exogenous C3a rescued organoid growth from C3-/- mice but not from C3aR1-/- mice. C3 is expressed in Lgr5+ intestinal stem cells and C3aR1 on various intestinal cells. C3-/- and C3aR1-/- mouse intestinal organoid assays, Lgr5.egfp reporter mice, C3aR1 deficiency rescue experiments, ischemia/reperfusion injury model Frontiers in immunology High 28928734
2017 C3aR and C5aR1 activation potentiates glucose-induced insulin secretion from human and mouse islets, increases intracellular calcium and ATP generation, and protects islets against apoptosis induced by pro-apoptotic cytokines or palmitate. Conditioned media from glucose-stimulated islets activates C3aR-driven β-arrestin recruitment. Radioimmunoassay for insulin, intracellular calcium measurement, ATP assay, β-arrestin recruitment assay, apoptosis assay in human and mouse islets Cellular and molecular life sciences Medium 28921001
2018 C3a/C3aR signaling in platelets regulates platelet adhesion, spreading, Ca2+ influx, and thrombus formation by activating the small GTPase Rap1b. C3aR-/- mice showed altered bleeding time and reduced thrombosis; reconstitution of C3aR-/- mice with C3aR+/+ platelets rescued thrombosis phenotype, demonstrating the platelet-specific mechanism. C3aR-/- mice were less prone to experimental stroke and myocardial infarction. C3aR-/- mice, platelet depletion/reconstitution experiments, intravital microscopy, in vitro platelet function tests, nano-LC-MS/MS for Rap1b identification, in vivo disease models Circulation High 29802205
2018 C3a-C3aR signaling promotes development of thoracic aortic dissection by upregulating MMP2 expression in smooth muscle cells. C3aR knockout inhibited BAPN-induced TAD formation; recombinant C3a stimulation enhanced MMP2 expression in mechanically stretched smooth muscle cells; MMP2-knockdown mice showed reduced TAD formation. C3aR-/- mice in BAPN model, C3aR antagonist treatment, recombinant C3a stimulation of SMCs, MMP2 KD via AAV-shRNA in vivo, histology Journal of immunology High 29367209
2018 C3aR1 deletion in PS19 tauopathy mice rescues tau pathology and attenuates neuroinflammation, synaptic deficits, and neurodegeneration. Mechanistically, STAT3 was identified as a direct downstream target of C3-C3aR signaling that functionally mediates tau pathogenesis. C3aR deletion inactivates a transcription factor network that drives disease-associated microglia and neurotoxic astrocyte signatures. C3ar1-/- PS19 mice, RNA sequencing, cell-type-specific transcriptomic analysis, histological assessment of tau pathology, synaptic and neurodegenerative markers Neuron High 30415998
2019 C3aR1 controls BM neutrophil mobilization after spinal cord injury by acting as a physiological antagonist of CXCR2-driven neutrophil mobilization. C3aR1 engages PTEN (a negative regulator of PI3K/AKT) to restrain CXCR2-driven neutrophil egress from bone marrow. C3aR1-/- mice showed exaggerated neutrophil mobilization and worse SCI outcomes. C3aR1-/- mice in SCI model, PTEN/PI3K/AKT signaling analysis, pharmacological CXCR2 antagonism, human SCI correlation data JCI insight High 31045582
2019 VEGFR2 survival and mitotic signaling in endothelial cells requires concurrent C3aR1/C5aR1 and IL-6R-gp130 co-signaling. C3aR1/C5aR1 blockade abolished VEGFR2 auto-phosphorylation and downstream Src, ERK, AKT, mTOR, and STAT3 activation, as well as EC cell cycle entry. VEGF-A augmented production of C3a/C5a/IL-6 via a p-Tyk2/p-STAT3 mechanism. The four receptors (VEGFR2, C3aR1, C5aR1, IL-6R) were found to be physically interactive by co-IP, confocal microscopy, ligand pulldown, and BRET assays. Co-immunoprecipitation, confocal microscopy, BRET assay, ligand pulldown, C3aR1/C5aR1 blockade, signaling pathway analysis, in vivo retinal angiogenesis Journal of cell science High 30765465
2019 Autocrine C3aR1 signaling in B2 cells is required for antibody production and class switch recombination (CSR). C3ar1-deficient mice immunized with OVA produced IgM but no other isotypes. CD40 upregulation, IL-6 production, BAFF/APRIL-driven growth, AID/Bcl-6 expression, and CD21 production all depended on B2 cell-intrinsic C3aR1/C5aR1 signaling. B2 cells themselves produced factor I and C3 to generate the autocrine signal. C3ar1-/- mice, μMT recipients of WT/C3ar1-/- B2 cells, C3-/- recipients with WT bone marrow, OVA/HEL immunization, adoptive transfer experiments Journal of immunology High 31217324
2019 Recipient C3aR1 signaling promotes alloreactive CD8+ T cell expansion and differentiation by two mechanisms: (1) T cell-intrinsic C3aR1 drives CD8+ T cell proliferation, mTOR activation, and T-bet expression; (2) host C3aR1 amplifies APC costimulatory molecule expression and innate cytokine production to indirectly facilitate CD8+ T cell expansion. C3ar1-/- mice cardiac allograft model, reciprocal adoptive transfer of WT/C3ar1-/- CD8+ T cells, pharmacological C3aR1 blockade, mTOR and T-bet signaling analysis American journal of transplantation High 30565852
2019 C3aR signaling inhibits NK cell infiltration into the tumor microenvironment. C3aR directly interacts with LFA-1 on activated NK cells, inducing a high-affinity LFA-1 conformation that decreases NK cell migration into tumors. Blocking C3aR signaling increased NK cell infiltration and led to tumor regression. C3aR-LFA-1 interaction studies, C3aR blockade in mouse tumor models, NK cell migration assays, LFA-1 conformation analysis Cancer immunology research Medium 34819308
2020 C3aR on microglia mediates white matter injury after chronic cerebral hypoperfusion. Genetic deletion of C3ar1 significantly inhibited aberrant microglial activation and reversed white matter injury, and C3aR antagonist SB290157 decreased microglial adherence to myelin and attenuated white matter injury and cognitive deficits in rats. C3aR-/- mice in bilateral carotid artery occlusion model, SB290157 pharmacological treatment in rats, CLARITY imaging, immunohistochemistry, behavioral testing Theranostics High 31903107
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 signaling activation. Genetic and pharmacological C3aR blockade in mouse breast cancer models, ex vivo cytokine/ECM assays, PI3K-AKT signaling analysis Journal of experimental & clinical cancer research Medium 31931851
2020 The C3-C3aR pathway mediates microglia-astrocyte interaction following status epilepticus. In C3-/- and C3aR-/- mice, microglia-astrocyte interaction was significantly reduced in response to kainic acid-induced status epilepticus, and C3-/- mice showed less neurodegeneration, identifying C3aR-dependent glial crosstalk as a contributor to KA-induced neurodegeneration. C3-/- and C3aR-/- mice in kainic acid status epilepticus model, microglial ablation, immunohistochemistry, spatial interaction analysis Glia High 33314324
2020 C3aR depletion in microglia reverses HIF-1α-induced metabolic impairment in Alzheimer's disease context. C3ar1-null microglia had lower HIF-1α expression, were resistant to hypoxia mimetic-induced metabolic changes and lipid droplet accumulation, and showed improved receptor recycling and Aβ phagocytosis. Crossing C3ar1-KO with APP-KI mice rescued dysregulated lipid profiles and improved microglial phagocytic and clustering abilities, identifying a C3aR/HIF-1α signaling axis governing microglial metabolic homeostasis. C3ar1 KO × APP-KI mice, primary microglial cultures, HIF-1α expression analysis, lipid droplet/metabolism assays, phagocytosis assays, synaptic/cognitive functional tests The Journal of clinical investigation High 37317973
2021 Complement C3aR (but not C5aR1 or C5aR2) deficiency mirrors C3 deficiency in reducing sarcoma growth. C3aR deficiency was associated with reduced tumor-associated macrophage accumulation, a shift to MHC II-dependent antigen presentation pathway in macrophages, and increased T cell activation and response to anti-PD-1 therapy, identifying the lectin pathway → C3aR axis as a key mediator of macrophage-driven immunosuppression in sarcomas. C3aR-/-, C3-/-, MBL1/2-/-, C4-/-, C5aR1-/-, C5aR2-/- mice in sarcoma models, transcriptional profiling of tumor-infiltrating macrophages, anti-PD-1 combination therapy Nature cancer High 34505065
2021 C3aR-/- mice display increased innate (unconditioned) anxiety, independent of C3a (the canonical ligand), suggesting an alternative ligand mediates this phenotype. This is mechanistically distinct from C3-/- mice which show increased conditioned fear via iC3b/CR3 signaling, demonstrating that C3 and C3aR control dissociable emotional behaviors through different signaling mechanisms. C3aR-/- and C3-/- mice, anxiety and fear conditioning behavioral assays Brain, behavior, and immunity Medium 34543680
2021 The reported C3aR antagonist SB290157 is actually a potent C3aR agonist in transfected cells and a partial C5aR2 agonist (β-arrestin recruitment) in both transfected cells and primary human and mouse macrophages, where SB290157 dampens C5a-induced ERK signaling via C5aR2 agonism. SB290157 acts as an antagonist in primary human macrophages for C3aR, but as an agonist in transfected cells, demonstrating cell context-dependent pharmacology. β-arrestin recruitment assays, ERK signaling assays, primary macrophage studies, C3aR/C5aR1/C5aR2 transfected cell models Frontiers in pharmacology High 33551801
2022 IL-1R/NF-κB signaling in astrocytes drives C3 release, which activates microglial C3aR, triggering hyperactivation of the microglial APT2/DHHC7 palmitoylation cycle, STAT3 translocation, and proinflammatory cytokine expression, leading to abnormal synaptic pruning in the prefrontal cortex in depression. C3aR blockade inhibited this cascade. LPS and chronic stress mouse models, C3aR antagonist treatment, proteomic analysis, APT2/DHHC7 palmitoylation cycle assay, STAT3 translocation assay, synaptic density analysis Cell & bioscience Medium 35715851
2022 C3aR signaling inhibits NK cell infiltration into tumors through direct physical interaction between C3aR and LFA-1, inducing high-affinity LFA-1 conformation and reduced NK cell migration. Blocking C3aR increased NK-cell TME infiltration and caused tumor regression in mouse models. C3aR-LFA-1 co-localization/interaction, LFA-1 conformation assay, C3aR blockade in tumor mouse models, NK cell migration assays Cancer immunology research Medium 34819308
2022 C3aR on dorsal root ganglion (DRG) macrophages mediates paclitaxel-induced peripheral neuropathic pain by upregulating TRPV4 on DRG neurons and promoting DRG macrophage expansion. C3aR1-/- mice showed less mechanical allodynia, reduced TRPV4 expression, and less macrophage expansion. C3aR1 antagonist in TRPV4 KO mice provided additional protection, indicating C3aR1 acts upstream of TRPV4. C3aR1-/- mice, C3aR1 antagonist treatment, TRPV4 KO mice, DRG macrophage expansion analysis, TRPV4 expression, neuron excitability measurement, intraepidermal nerve fiber density Journal of immunology High 37861348
2022 C3aR contributes to renal interstitial fibrosis by promoting NLRP3 inflammasome assembly in renal tubular epithelial cells. C3aR-/- mice showed attenuated renal fibrosis and reduced NLRP3 inflammasome activation after UUO. NLRP3 inhibition (MCC950) did not affect C3aR expression, placing C3aR upstream of the NLRP3 inflammasome. C3aR-/- mice in UUO model, MCC950 NLRP3 inhibitor, Western blot, immunohistochemistry, renal function assays Life sciences Medium 36041502
2023 C3a-bound C3aR and apo-C3aR structures were determined. The structures reveal: (1) a conserved recognition pattern for anaphylatoxin binding that differs from chemokine receptors; (2) unique pocket topologies of C3aR mediating ligand selectivity; and (3) a common activation mechanism for C3aR and C5aR1. Mutagenesis validated key contact residues. Cryo-EM/X-ray crystallography of C3a-bound C3aR, apo-C3aR, and C5a-bound C5aR1; site-directed mutagenesis Nature chemical biology High 37169960
2023 C3aR1 preferentially couples to Gi/o/z proteins and recruits β-arrestins to cause receptor internalization. Compared to C3a63-77, TLQP-21 exhibits biased agonism toward Gi/o-mediated signaling over β-arrestin recruitment/internalization. SB290157 is a potent C3aR1 agonist that antagonizes ligand-stimulated calcium flux through potent β-arrestin-mediated receptor internalization. Signaling bias has functional consequences for calcium influx, lipolysis in adipocytes, phagocytosis in microglia, and mast cell degranulation. BRET-based G protein coupling assays, β-arrestin recruitment assays, receptor internalization assays, calcium flux measurements, adipocyte lipolysis, microglial phagocytosis, mast cell degranulation assays The Journal of biological chemistry High 38072064
2023 C3aR1 on macrophages is critical for rapid capture of pathogenic fungi (Histoplasma capsulatum, Candida albicans, Coccidioides posadasii) but is dispensable for phagocytosis of bacteria and latex beads. C3aR1 localizes to the early phagosome during H. capsulatum infection and coordinates formation of actin-rich membrane protrusions that promote fungal capture. The ER membrane complex (EMC) promotes surface expression of C3aR, thus enabling this function. Genome-scale CRISPR-Cas9 screen, C3aR KO validation, phagocytosis assays with bacteria/beads/fungi, phagosomal localization imaging, actin protrusion analysis, EMC-C3aR epistasis PLoS pathogens High 36174103
2023 C3a/C3aR activation promotes EMT in renal tubular epithelial cells synergistically with TGF-β via ERK-mediated NLRP3 inflammasome assembly. C3aR inhibition attenuated EMT and NLRP3 activation; ERK inhibition blocked NLRP3 activation but not C3aR expression, placing ERK downstream of C3aR and upstream of NLRP3 in a C3aR→ERK→NLRP3→EMT pathway. C3aR antagonist, NLRP3 inhibitor MCC950, ERK inhibitor PD98059 in TCMK-1 cells; C3aR-/- mice in UUO model; Western blot, immunofluorescence, ELISA Journal of translational medicine Medium 38082306
2023 C3aR in astrocytes mediates chronic post-thoracotomy pain by inducing neurotoxic A1 astrocyte polarization, while also influencing M1 microglial activation. Intrathecal AAV-mediated knockdown of C3aR specifically in astrocytes (GFAP promoter) inhibited LPS-induced A1 activation, decreased M1 microglia, and alleviated chronic pain. C3aR downregulation also increased anti-inflammatory A2 astrocyte numbers. Rat thoracotomy pain model, AAV2/9-rC3ar1 shRNA-GFAP intrathecal injection, single-cell RNA sequencing, RT-PCR, Western blot, immunofluorescence, behavioral pain assessment Biochimica et biophysica acta. Molecular basis of disease Medium 36871753
2023 Renin cleaves C3 into C3a which activates C3aR on renal tubular epithelial cells, impairing PPARα/CPT-1α-mediated mitochondrial fatty acid oxidation and inducing a profibrotic phenotype. C3aR antagonist SB290157 restored mitochondrial FAO and alleviated tubulointerstitial fibrosis in 2K1C hypertensive rats. In vitro renin-C3 cleavage assay (ELISA), HK2 cell C3a/C3aR antagonist experiments, 2K1C rat model, PPARα/CPT-1α pathway analysis, Western blot Frontiers in bioscience Medium 37919077
2023 In NPM1-mutated AML cells, C3AR stimulation with C3a activates ERK1/2 and promotes AML cell survival. Anti-C3AR antibodies efficiently elicit NK cell-mediated killing of primary AML cells ex vivo. Flow cytometry, scRNA sequencing, C3a stimulation/ERK1/2 phosphorylation assay, NK cell cytotoxicity assay, xenotransplantation into immunodeficient mice Blood advances Medium 36383712
2024 C3aR activation exacerbates early brain injury after subarachnoid hemorrhage via the C3aR→ERK→P2X7→NLRP3 inflammasome signaling axis. C3a promotes ATP efflux through ERK1/2 phosphorylation, which activates P2X7 receptor, which in turn activates the NLRP3 inflammasome. C3aR inhibition (SB290157) reduced inflammasome activation, neuroinflammation, and improved outcomes in SAH mice. ERK inhibitor, P2X7R antagonist (JNJ-55308942), C3aR inhibitor (SB290157) in BV-2 cells and SAH mouse model; Western blot, ELISA, behavioral analysis, ATP release assay Inflammation Medium 39528767
2024 Adipocyte-specific C3aR1 knockout in male mice enhances white adipose tissue thermogenesis and increases respiration, whereas female adipocyte-specific C3aR1-KO mice display decreased brown fat thermogenesis and cold intolerance, revealing sexual dimorphism in the adipsin/C3a/C3aR1 axis. Female mice express lower levels of Adipsin in thermogenic adipocytes and lower C3aR1 in subcutaneous adipose tissue than males. Adipocyte-specific C3aR1-KO mice (male and female), Adipsin/Cfd-KO mice, energy expenditure measurement, cold tolerance test, adipose thermogenesis assessment JCI insight High 38713526
2024 In a membranous nephropathy glomerulus-on-a-chip model, C3aR activation on podocytes (not membrane attack complex formation) is the critical mechanism of complement-mediated albumin permselectivity loss. C3AR gene silencing or C3aR antagonism reduced oxidative stress and prevented albumin leakage, whereas MAC inhibition did not. C3aR antagonist prevented proteinuria in a mouse MN model. Glomerulus-on-a-chip with primary human podocytes, C3AR siRNA knockdown, C3aR antagonist, MAC inhibitor, in vivo mouse MN model with C3aR antagonist JCI insight High 38227377
2024 In glioma, NFAT1 in tumor-associated macrophages transcriptionally upregulates C3 and increases C3a secretion; C3a 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 for M2 polarization, which promotes mesenchymal glioma stem cell transition. Nfat1-/- mice glioma model, C3 transcriptional activity assay, TIM-3 pathway analysis, Ca2+-NFAT1 signaling assay, C3aR inhibitor in vitro and in vivo Cancer immunology research Medium 38289255
2024 C3aR modulates susceptibility to depressive-like behaviors through mPFC glutamatergic neuronal excitability. C3aR deletion or intra-mPFC antagonism confers resilience; C3aR-null mPFCGlu neurons display hyperexcitability upon LPS treatment, which is anti-depressant. C3aR expression in mPFC neurons makes KO mice susceptible when C3aR is reintroduced, identifying C3aR as a direct modulator of glutamatergic neuronal excitability. C3aR KO mice, intra-mPFC C3aR antagonism, viral C3aR re-expression in KO mPFC neurons, mPFCGlu neuron-specific excitability assays (electrophysiology), LPS depression model Progress in neurobiology High 38641040
2024 Astrocyte-derived C3, induced via TLR2/NF-κB signaling by α-synuclein PFFs, signals to dopaminergic neurons via C3aR to influence neuronal apoptosis and α-synuclein pathology potentially through GSK3β modulation. Overexpression of C3 exacerbated, and downregulation of C3 protected against, motor dysfunction and dopaminergic neuron loss in PFF-injected mice. AAV-mediated C3 overexpression/knockdown in PFF-injected mice, TLR2/NF-κB inhibitor treatment in primary astrocytes, astrocyte-neuron co-culture C3/C3aR pathway analysis, GSK3β signaling Brain, behavior, and immunity Medium 39288893

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 406 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 257 23263555
2016 Coagulation induced by C3aR-dependent NETosis drives protumorigenic neutrophils during small intestinal tumorigenesis. Nature communications 214 26996437
2020 Microglia exacerbate white matter injury via complement C3/C3aR pathway after hypoperfusion. Theranostics 172 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 130 8765043
2020 The complement C3-C3aR pathway mediates microglia-astrocyte interaction following status epilepticus. Glia 127 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 120 23118029
2023 Helicobacter pylori-derived outer membrane vesicles contribute to Alzheimer's disease pathogenesis via C3-C3aR signalling. Journal of extracellular vesicles 116 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 94 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 83 23940034
2020 VGF-derived peptide TLQP-21 modulates microglial function through C3aR1 signaling pathways and reduces neuropathology in 5xFAD mice. Molecular neurodegeneration 77 31924226
2017 Monitoring C3aR Expression Using a Floxed tdTomato-C3aR Reporter Knock-in Mouse. Journal of immunology (Baltimore, Md. : 1950) 74 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 73 26956419
2019 The Complement Receptors C3aR and C5aR Are a New Class of Immune Checkpoint Receptor in Cancer Immunotherapy. Frontiers in immunology 71 31379815
2019 Complement receptor C3aR1 controls neutrophil mobilization following spinal cord injury through physiological antagonism of CXCR2. JCI insight 70 31045582
2022 IL-1R/C3aR signaling regulates synaptic pruning in the prefrontal cortex of depression. Cell & bioscience 61 35715851
2021 Complement activation promoted by the lectin pathway mediates C3aR-dependent sarcoma progression and immunosuppression. Nature cancer 61 34505065
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
2020 C3a-C3aR signaling promotes breast cancer lung metastasis via modulating carcinoma associated fibroblasts. Journal of experimental & clinical cancer research : CR 58 31931851
2023 Complement C3aR depletion reverses HIF-1α-induced metabolic impairment and enhances microglial response to Aβ pathology. The Journal of clinical investigation 56 37317973
2008 Role of complement anaphylatoxin receptors (C3aR, C5aR) in the development of the rat cerebellum. Molecular immunology 55 18635264
2023 Revealing the signaling of complement receptors C3aR and C5aR1 by anaphylatoxins. Nature chemical biology 53 37169960
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
2018 The Complement C3a-C3aR Axis Promotes Development of Thoracic Aortic Dissection via Regulation of MMP2 Expression. Journal of immunology (Baltimore, Md. : 1950) 46 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 40 34439277
2009 C3aR inhibition reduces neurodegeneration in experimental lupus. Lupus 39 19900981
2023 Cntnap4 partial deficiency exacerbates α-synuclein pathology through astrocyte-microglia C3-C3aR pathway. Cell death & disease 38 37087484
2017 C3aR and C5aR1 act as key regulators of human and mouse β-cell function. Cellular and molecular life sciences : CMLS 38 28921001
2016 The neuropeptide TLQP-21 opposes obesity via C3aR1-mediated enhancement of adrenergic-induced lipolysis. Molecular metabolism 37 28123945
2014 The receptor for the complement C3a anaphylatoxin (C3aR) provides host protection against Listeria monocytogenes-induced apoptosis. Journal of immunology (Baltimore, Md. : 1950) 34 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 33 31865842
2015 Complement anaphylatoxin receptors C3aR and C5aR are required in the pathogenesis of experimental autoimmune uveitis. Journal of leukocyte biology 33 26394814
2021 The "C3aR Antagonist" SB290157 is a Partial C5aR2 Agonist. Frontiers in pharmacology 31 33551801
2021 C3/C3aR inhibition alleviates GMH-IVH-induced hydrocephalus by preventing microglia-astrocyte interactions in neonatal rats. Neuropharmacology 31 34921829
2020 Protective Role of C3aR (C3a Anaphylatoxin Receptor) Against Atherosclerosis in Atherosclerosis-Prone Mice. Arteriosclerosis, thrombosis, and vascular biology 28 32762445
2024 An NFAT1-C3a-C3aR Positive Feedback Loop in Tumor-Associated Macrophages Promotes a Glioma Stem Cell Malignant Phenotype. Cancer immunology research 27 38289255
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
2019 Follicular B2 Cell Activation and Class Switch Recombination Depend on Autocrine C3ar1/C5ar1 Signaling in B2 Cells. Journal of immunology (Baltimore, Md. : 1950) 27 31217324
2017 C3a Enhances the Formation of Intestinal Organoids through C3aR1. Frontiers in immunology 27 28928734
2024 Transcriptome Analysis Reveals Dynamic Microglial-Induced A1 Astrocyte Reactivity via C3/C3aR/NF-κB Signaling After Ischemic Stroke. Molecular neurobiology 26 38713438
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 Astrocyte-neuron communication through the complement C3-C3aR pathway in Parkinson's disease. Brain, behavior, and immunity 23 39288893
2022 Astrocyte-microglia interaction through C3/C3aR pathway modulates neuropathic pain in rats model of chronic constriction injury. Molecular pain 23 36341694
2021 Complement C3 and C3aR mediate different aspects of emotional behaviours; relevance to risk for psychiatric disorder. Brain, behavior, and immunity 23 34543680
2021 C3aR Signaling Inhibits NK-cell Infiltration into the Tumor Microenvironment in Mouse Models. Cancer immunology research 23 34819308
2023 Microglia refine developing retinal astrocytic and vascular networks through the complement C3/C3aR axis. Development (Cambridge, England) 22 36762625
2020 Aristolochic acid I promotes the invasion and migration of hepatocellular carcinoma cells by activating the C3a/C3aR complement system. Toxicology letters 22 32898628
2022 Gypenoside XVII, an Active Ingredient from Gynostemma Pentaphyllum, Inhibits C3aR-Associated Synaptic Pruning in Stressed Mice. Nutrients 21 35745148
2023 Functional profiling of the G protein-coupled receptor C3aR1 reveals ligand-mediated biased agonism. The Journal of biological chemistry 20 38072064
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
2019 VEGFR2 survival and mitotic signaling depends on joint activation of associated C3ar1/C5ar1 and IL-6R-gp130. Journal of cell science 19 30765465
2024 C3aR-initiated signaling is a critical mechanism of podocyte injury in membranous nephropathy. JCI insight 18 38227377
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 18 35837068
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
2024 Adipsin and adipocyte-derived C3aR1 regulate thermogenic fat in a sex-dependent fashion. JCI insight 16 38713526
2024 Complement C3aR signaling: Immune and metabolic modulation and its impact on Alzheimer's disease. European journal of immunology 16 38778507
2023 Complement Activation and Up-Regulated Expression of Anaphylatoxin C3a/C3aR in Glioblastoma: Deciphering the Links with TGF-β and VEGF. Cancers 16 37174113
2022 Complement C3a Enhances the Phagocytic Activity of B Cells Through C3aR in a Fish. Frontiers in immunology 16 35386704
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
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 15 34403734
2020 Down-Regulation of C3aR/C5aR Inhibits Cell Proliferation and EMT in Hepatocellular Carcinoma. Technology in cancer research & treatment 15 33176600
2024 Complement Molecule C3a Exacerbates Early Brain Injury After Subarachnoid Hemorrhage by Inducing Neuroinflammation Through the C3aR-ERK-P2X7-NLRP3 Inflammasome Signaling Axis. Inflammation 14 39528767
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 14 35503088
2022 C3aR contributes to unilateral ureteral obstruction-induced renal interstitial fibrosis via the activation of the NLRP3 inflammasome. Life sciences 14 36041502
2019 C3aR signaling and gliosis in response to neurodevelopmental damage in the cerebellum. Journal of neuroinflammation 14 31272467
2018 Expression of complement C3, C5, C3aR and C5aR1 genes in resting and activated CD4+ T cells. Immunobiology 14 30612786
2014 Downregulation of complement C3 and C3aR expression in subcutaneous adipose tissue in obese women. PloS one 14 24743347
2012 Participation of complement 3a receptor (C3aR) in the sensitization phase of Th2 mediated allergic contact dermatitis. Experimental dermatology 14 22151392
2022 Complement C3a Receptor (C3aR) Mediates Vascular Dysfunction, Hippocampal Pathology, and Cognitive Impairment in a Mouse Model of VCID. Translational stroke research 13 35258803
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
2025 C3/C3aR Bridges Spinal Astrocyte-Microglia Crosstalk and Accelerates Neuroinflammation in Morphine-Tolerant Rats. CNS neuroscience & therapeutics 12 39801259
2025 CD81+ senescent-like fibroblasts exaggerate inflammation and activate neutrophils via C3/C3aR1 axis in periodontitis. eLife 12 40801798
2023 Complement Receptor C3aR1 Contributes to Paclitaxel-Induced Peripheral Neuropathic Pain in Mice and Rats. Journal of immunology (Baltimore, Md. : 1950) 12 37861348
2022 C3aR plays both sides in regulating resistance to bacterial infections. PLoS pathogens 12 35925892
2024 Microglia aggravate white matter injury via C3/C3aR pathway after experimental subarachnoid hemorrhage. Experimental neurology 11 38866102
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 11 39218048
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 11 38082306
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 C3aR in the medial prefrontal cortex modulates the susceptibility to LPS-induced depressive-like behaviors through glutamatergic neuronal excitability. Progress in neurobiology 10 38641040
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
2017 Complement component C3aR constitutes a novel regulator for chick eye morphogenesis. Developmental biology 9 28576690
2023 The complement receptor C3AR constitutes a novel therapeutic target in NPM1-mutated AML. Blood advances 8 36383712
2023 C3aR Antagonist Alleviates C3a Induced Tubular Profibrotic Phenotype Transition via Restoring PPARα/CPT-1α Mediated Mitochondrial Fatty Acid Oxidation in Renin-Dependent Hypertension. Frontiers in bioscience (Landmark edition) 8 37919077
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

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