Affinage

FCGR1A

High affinity immunoglobulin gamma Fc receptor I · UniProt P12314

Length
374 aa
Mass
42.6 kDa
Annotated
2026-04-28
100 papers in source corpus 31 papers cited in narrative 31 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FCGR1A (CD64/FcγRI) is a high-affinity IgG receptor on myeloid cells that couples immune complex recognition to phagocytosis, antibody-dependent cellular cytotoxicity, antigen presentation, and inflammatory cytokine production. The ligand-binding α-chain, whose second and third extracellular domains confer high-affinity IgG binding (PMID:9881694), associates with the ITAM-bearing FcR γ-chain to activate a Syk/Shc/Grb2/Raf-1/ERK signaling cascade that drives phagocytosis, respiratory burst, and NF-κB/NLRP3-dependent IL-1β release (PMID:8662746, PMID:29920250); the α-chain cytoplasmic tail independently directs receptor–antigen complexes to MHC class II late endosomes and enables MHC class I cross-presentation, while its serine phosphorylation tonically regulates γ-chain ITAM signaling and phagocytosis kinetics (PMID:10397749, PMID:12200451, PMID:11223078). Cytokine-driven inside-out signaling reorganizes FcγRI into actin- and PP1-phosphatase-dependent nanoclusters that enhance ADCC (PMID:30042128), whereas inhibitory co-receptors LILRB4 and SHP-1 suppress FcγRI effector functions through broad tyrosine dephosphorylation of downstream signaling components (PMID:19833736, PMID:17227821). Beyond myeloid cells, FcγRI is expressed on joint sensory neurons where IgG immune complex crosslinking directly activates nociceptors to drive arthritis pain independently of inflammation (PMID:31211699).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1996 High

    Identification of the proximal signaling cascade downstream of FcγRI resolved how this receptor specifically activates the respiratory burst: cross-linking induces Raf-1 tyrosine phosphorylation and Shc–Grb2 complex formation with kinetics preceding functional output, a pathway unique among FcγRs.

    Evidence FcγRI cross-linking in IFN-γ-differentiated U937 cells; immunoprecipitation/western blot for Raf-1, Shc, Grb2; respiratory burst assay

    PMID:8662746

    Open questions at the time
    • Upstream kinase(s) directly phosphorylating Raf-1 downstream of FcγRI not identified
    • No direct link to ERK demonstrated in this study
  2. 1998 High

    Domain-swap mutagenesis established that the second and third extracellular domains of FcγRI are the structural determinants of high-affinity monomeric IgG binding, distinguishing it from low-affinity FcγRs and explaining its unique ligand-binding properties.

    Evidence Chimeric FcγRI/FcγRII receptors by domain exchange; IgG binding assays in transfected cells

    PMID:9881694

    Open questions at the time
    • Atomic-resolution contacts not defined until later crystallography
    • Contribution of receptor glycosylation to affinity not tested
  3. 1998 Medium

    The requirement for an intact γ-chain ITAM for FcγRI-mediated phagocytosis and ADCC was formally demonstrated, confirming that the γ-chain is the essential signaling subunit and that SLP-76, Cbl, and Shc participate as downstream adaptors.

    Evidence FcγRI reconstitution with wild-type or ITAM-mutant γ-chain in IIA1.6 cells; phagocytosis and ADCC assays; co-IP of SLP-76/Cbl/Shc complex in U937 cells

    PMID:9716598 PMID:9737671

    Open questions at the time
    • Relative contributions of individual ITAM tyrosines not dissected
    • No direct kinase–substrate relationships established for SLP-76 or Cbl
  4. 1999 High

    The α-chain cytoplasmic tail was shown to carry autonomous targeting information directing receptor–antigen complexes to MHC class II late endosomes and to regulate phagocytosis kinetics, calcium dependence, and IL-6 secretion independently of the γ-chain ITAM, establishing a dual-function model for FcγRI signaling.

    Evidence Cytoplasmic tail deletion/truncation mutants in IIA1.6 and P388D1 cells; immunoelectron microscopy; antigen presentation, phagocytosis, calcium flux, and cytokine secretion assays

    PMID:10397749 PMID:10514529

    Open questions at the time
    • Specific sorting motifs within the cytoplasmic tail not mapped to individual residues
    • Mechanism of calcium-independent phagocytosis not elucidated
  5. 2001 Medium

    FcγRI was demonstrated to mediate cross-presentation on MHC class I, expanding its antigen-presentation repertoire beyond MHC class II and identifying it as a route for CTL priming by myeloid cells.

    Evidence FcγRI-targeted PSA fusion protein on THP-1 cells; CTL cytotoxicity assay with receptor-blocking antibodies

    PMID:11223078

    Open questions at the time
    • Molecular pathway linking FcγRI internalization to MHC class I loading not defined
    • Contribution of proteasomal vs. vacuolar processing not tested
  6. 2002 High

    FcγRI knockout mice revealed the in vivo requirement for FcγRI in IgG2a immune complex-mediated phagocytosis, ADCC, antigen presentation, hypersensitivity, cartilage destruction in arthritis, and bacterial defense—establishing that FcγRI is non-redundant with other activating FcγRs in vivo.

    Evidence FcγRI−/− mouse models; phagocytosis, ADCC, antigen presentation assays; arthritis and bacterial infection models

    PMID:11911823 PMID:11911824

    Open questions at the time
    • Relative contributions of monocytes vs. macrophages vs. DCs to each phenotype not resolved
    • Compensatory changes in other FcγRs not fully assessed
  7. 2002 High

    Serine phosphorylation of the α-chain cytoplasmic domain was identified as a tonic regulatory mechanism governing γ-chain ITAM-dependent signaling: serine-to-alanine mutations abolished okadaic acid-sensitive inhibition of phagocytosis and the early tyrosine phosphorylation cascade.

    Evidence Serine-to-alanine mutagenesis of FcγRI cytoplasmic domain in P388D1 macrophages; okadaic acid treatment; phagocytosis and phospho-tyrosine assays

    PMID:12200451

    Open questions at the time
    • Identity of the serine kinase(s) responsible not determined
    • Specific serine residues mapped only partially
  8. 2004 High

    Periplakin was identified as a cytosolic partner of the FcγRI α-chain that enhances ligand binding, internalization, and MHC class II antigen presentation, revealing a novel cytoskeletal-associated regulatory axis for FcγRI.

    Evidence Mutagenesis of FcγRI and periplakin; TAT peptide inhibition of the interaction; rosetting and antigen presentation assays

    PMID:15161926

    Open questions at the time
    • Structural basis of periplakin–FcγRI interaction unknown
    • Whether periplakin regulates FcγRI on primary cells in vivo not tested
  9. 2007 High

    Two inhibitory checkpoints on FcγRI signaling were defined: LILRB4 co-ligation broadly dephosphorylates Syk, Lck, LAT, Erk, and Cbl to suppress TNF production, while immune complex-activated SHP-1 suppresses STAT1 phosphorylation to dampen IFN-γ signaling—establishing layered negative regulation of FcγRI effector functions.

    Evidence LILRB4/CD64 co-ligation on THP-1 monocytes with phospho-protein western blots and phosphatase inhibitors; STAT1 phosphorylation in FcR γ-chain KO and SHP-1 KO (motheaten) mouse cells

    PMID:17227821 PMID:19833736

    Open questions at the time
    • Identity of the LILRB4-recruited phosphatase(s) other than SHP-1 not established
    • Whether LILRB4 and SHP-1 pathways converge or operate independently unknown
  10. 2010 High

    FcγRI was found to serve as a direct entry receptor for E. coli K1 via OmpA binding to the α-chain, independent of IgG opsonization, establishing a pathogen subversion mechanism; FcγRI−/− mice resist E. coli K1 meningitis.

    Evidence COS-1 overexpression of full-length vs. C-terminal truncated FcγRI; FcγRI−/− mouse infection model; adoptive macrophage transfer; co-IP and phospho-tyrosine analysis

    PMID:21124939

    Open questions at the time
    • Precise OmpA binding site on FcγRI α-chain not mapped
    • Whether other bacteria exploit this pathway not tested
  11. 2018 High

    Cytokine-induced inside-out signaling was shown to reorganize FcγRI into nanoclusters via an actin- and PP1-phosphatase-dependent mechanism, enhancing ADCC—revealing that FcγRI effector potency is tuned by receptor spatial organization rather than expression level alone.

    Evidence STORM super-resolution imaging of FcγRI clustering on neutrophils; PP1 and actin inhibitors; ADCC assay against CD20+ tumor cells

    PMID:30042128

    Open questions at the time
    • PP1 substrate(s) controlling clustering not identified
    • Whether nanoclustering affects antigen presentation not tested
  12. 2019 High

    FcγRI was discovered on joint sensory neurons, where IgG immune complex crosslinking directly activates nociceptors to drive arthritis pain independently of inflammation—extending FcγRI function beyond the immune system to the nervous system.

    Evidence Global and sensory-neuron-specific Fcgr1 conditional KO mice; ex vivo electrophysiology; behavioral pain assays in multiple arthritis models

    PMID:31211699

    Open questions at the time
    • Downstream signaling pathway in neurons not fully characterized
    • Whether neuronal FcγRI associates with FcR γ-chain or signals independently unknown
  13. 2023 Medium

    The neuronal FcγRI pain axis was extended to neuropathic pain: CRP activates neuronal FcγRI after nerve injury via a positive-feedback proinflammatory loop, and naive IgG competing for FcγRI suppresses this activation and alleviates pain.

    Evidence Fcgr1 conditional KO in rat DRG neurons; CRP and naive IgG microinjection into DRG; behavioral pain assays and signaling analysis

    PMID:36727833

    Open questions at the time
    • CRP binding site on FcγRI not mapped
    • Whether CRP/FcγRI signaling uses ITAM-dependent or independent pathway not resolved
    • Single lab finding, not independently confirmed

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the identity of the serine kinase(s) and PP1 substrates that control α-chain phosphorylation and nanocluster formation, the structural basis for dual γ-chain-dependent and -independent signaling from the same receptor, and the full signaling pathway mediating neuronal FcγRI-driven nociception.
  • No serine kinase identified for α-chain cytoplasmic tail
  • Structural model of full-length FcγRI in complex with γ-chain lacking
  • Neuronal FcγRI signaling pathway incompletely defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005886 plasma membrane 3 GO:0005768 endosome 2 GO:0031410 cytoplasmic vesicle 2
Pathway
R-HSA-168256 Immune System 7 R-HSA-162582 Signal Transduction 6 R-HSA-1643685 Disease 3 R-HSA-5653656 Vesicle-mediated transport 2
Partners
CBLFCER1GGRB2LILRB4PPLSHC1SLP76SYK
Complex memberships
FcγRI α-chain / FcR γ-chain signaling complex

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 The FcγRIa (CD64) ligand-binding α-chain cytoplasmic tail contains autonomous targeting information directing receptor-antigen complexes to MHC class II-containing late endosomes for antigen presentation, independently of the FcR γ-chain ITAM. Radical deletion of the cytoplasmic tail diverted receptor-ligand complexes to the recycling pathway and decreased antigen presentation, demonstrating γ-chain-independent MHC class II presentation by FcγRIa. Cell transfection with cytoplasmic-tail deletion mutants, immunoelectron microscopy tracking of receptor-antigen complexes, MHC class II antigen presentation assay in IIA1.6 cell model Blood High 10397749
1999 The FcγRIa extracellular domain is sufficient for internalization of infectious dengue virus immune complexes; deletion of the FcγRIa cytoplasmic domain had no effect on receptor-mediated immune complex infectivity, demonstrating that classical ITAM-dependent signaling is not required for this internalization event. COS cell transfection with native and cytoplasmic-domain-truncated FcγRIa (±γ-chain), plaque assay for dengue virus replication Virology Medium 10405359
1999 The cytoplasmic domain (CY) of the FcγRIa α-chain directly alters the functional properties of the FcγRIa/γ-chain receptor complex: deletion of CY slows phagocytosis and endocytosis kinetics, converts calcium-independent phagocytosis to calcium-dependent, and abrogates IL-6 (but not IL-1β) secretion without affecting receptor surface expression. Stable transfection of full-length vs. CY-deletion mutants of human FcγRIa in mouse macrophage P388D1 cells; phagocytosis, endocytosis kinetics, calcium flux, cytokine secretion assays The Journal of biological chemistry High 10514529
1998 The second and third extracellular domains of FcγRI together confer unique high-affinity monomeric IgG2a binding; domain 1 plays a supporting role in conformational stability. Chimeric receptors replacing domains 1+2 with FcγRII equivalents abolished high-affinity binding; restoring domain 2 of FcγRI (keeping domain 1 of FcγRII) reconstituted high-affinity IgG2a binding. Generation of chimeric FcγRI/FcγRII receptors by domain exchange, transfection and IgG binding assays Molecular immunology High 9881694
1996 FcγRI cross-linking in IFN-γ-differentiated U937 cells induces tyrosine phosphorylation of Raf-1 (10-fold increase, peaking 1-2 min post-stimulation), recruits Shc-Grb2 complex formation, and precedes activation of the respiratory burst; this signaling is unique to FcγRI and not triggered by FcγRII, FcγRIII, PMA, fMLP, or other stimuli. FcγRI cross-linking in U937IF cells, immunoprecipitation and western blotting for Raf-1 phosphorylation, Shc-Grb2 co-immunoprecipitation, respiratory burst assay The Journal of biological chemistry High 8662746
1998 FcγRI stimulation induces tyrosine phosphorylation of SLP-76, Cbl, and Shc, and promotes formation of a multimolecular SLP-76–Cbl–Shc–Grb2 complex; a phosphorylation-dependent SLP-76–Shc interaction is induced ≥10-fold by FcγRI aggregation, identifying SLP-76 and Cbl as components of FcγRI signal relay. FcγRI cross-linking in U937IF cells, co-immunoprecipitation, phospho-tyrosine western blotting Blood Medium 9716598
2002 Serine phosphorylation of the FcγRIa α-chain cytoplasmic domain is a critical regulatory mechanism: truncation or serine-to-alanine mutation of the cytoplasmic domain abolished okadaic-acid-sensitive inhibition of phagocytosis and the early tyrosine phosphorylation cascade, demonstrating that α-chain serine phosphorylation regulates γ-chain ITAM-dependent signaling. Mutagenesis of cytoplasmic serine residues in human FcγRIa variants expressed in P388D1 macrophages; okadaic acid inhibition experiments; phagocytosis and tyrosine phosphorylation assays The Journal of biological chemistry High 12200451
2002 FcγRI−/− mice display impaired endocytosis of monomeric IgG, reduced kinetics of immune complex phagocytosis, defective macrophage ADCC, and impaired immune complex-dependent antigen presentation to primed T cells; FcγRI also controls antibody response magnitude and can function partially without the FcR γ-chain. FcγRI knockout mouse model, phagocytosis assays, ADCC assays, antigen presentation assays, serum antibody measurements Immunity High 11911823
2002 FcγRI contributes substantially to IgG2a immune complex-induced phagocytosis, cytokine release, cellular cytotoxicity, and antigen presentation in vivo; FcγRI−/− mice show impaired hypersensitivity responses, strongly reduced cartilage destruction in arthritis, and impaired protection from bacterial infection. FcγR-knockout mouse panel; hypersensitivity models, immune arthritis model, bacterial infection protection assay Immunity High 11911824
2004 Periplakin C-terminus selectively interacts with the FcγRI α-chain cytoplasmic domain and enhances FcγRI capacity to bind, internalize, and present antigens on MHC class II. TAT peptides disrupting this endogenous FcγRI–periplakin interaction modulate FcγRI ligand binding, establishing periplakin as a novel cytosolic regulator of FcγRI function. Truncation and alanine-substitution mutagenesis of FcγRI and periplakin; TAT peptide inhibition; erythrocyte-antibody rosetting assay; antigen presentation assay The Journal of biological chemistry High 15161926
2004 IFN-γ-induced FcγRI (CD64) expression on human mast cells enables their activation by aggregated IgG1 (but not IgG2/3/4), leading to degranulation (β-hexosaminidase release), PGD2, LTC4, IL-3, IL-13, GM-CSF, and TNFα production; C3a produces additive degranulation. Blocking FcγRI with F(ab')2 reduces IgG1-mediated degranulation by 38%. IFN-γ priming of human mast cells, aggregated IgG stimulation, β-hexosaminidase release assay, receptor-blocking antibody experiments, eicosanoid and cytokine measurements Clinical immunology Medium 15003814
2006 FcγRIa ITAM signaling (via γ-chain) is required for both phagocytosis and dengue virus immune complex infectivity enhancement; abrogating FcγRIa signaling competency (by expression without γ-chain or with ITAM tyrosine mutant γ-chain) impairs both phagocytosis and dengue IC infectivity, whereas FcγRIIa ITAM abrogation impairs phagocytosis but not infectivity—demonstrating fundamental mechanistic differences between the two receptors. Site-directed mutagenesis of ITAM tyrosine residues; COS-7 transfection with native/signaling-incompetent receptor variants; plaque assay; flow cytometry for dengue replication Journal of virology High 17005690
2007 In immature neutrophils, FcγRI (CD64) has a weaker association with the FcR γ-chain than FcαRI does, resulting in absent FcγRI-mediated γ-chain-dependent functions (ADCC, respiratory burst, calcium mobilization, MAPK phosphorylation) while γ-chain-independent internalization proceeds normally via both receptors. Co-immunoprecipitation of FcγRI and FcαRI with FcR γ-chain in mature vs. immature neutrophils; calcium mobilization, MAPK phosphorylation, ADCC, respiratory burst assays Journal of immunology Medium 17709506
2007 Immune complexes inhibit IFN-γ–induced STAT1 phosphorylation through FcγRI: IC-mediated inhibition is reduced in FcR common γ-chain knockout cells, and requires the phosphatase SHP-1 (as shown by motheaten SHP-1 KO cells), suppressing STAT1 without blocking STAT1 binding to the IFN-γ receptor. Pull-down assays for STAT1 phosphorylation; real-time RT-PCR for IFN-inducible genes; experiments with FcR γ-chain KO and SHP-1 KO (motheaten) mouse cells Journal of leukocyte biology Medium 17227821
2009 LILRB4 (LILRB4) potently inhibits FcγRI (CD64)-mediated TNFα production by dephosphorylating Lck, Syk, LAT, Erk, and c-Cbl (but not α-actinin-4) upon co-ligation with CD64 on monocytes; LILRB4 aggregates to sites of FcγRI activation, and its inhibitory effect is reversed by broad phosphatase inhibitor (pervanadate) but not by the SHP-1-specific inhibitor sodium stibogluconate, implicating phosphatases other than SHP-1. Co-ligation of LILRB4 and CD64 on THP-1 cells; TNFα ELISA; western blotting for phosphorylated Lck, Syk, LAT, Erk, c-Cbl, α-actinin-4; pharmacological phosphatase inhibition The Journal of biological chemistry High 19833736
2010 FcγRI α-chain cytoplasmic tail interaction with the outer membrane protein A (OmpA) of E. coli K1 enables bacterial entry into macrophages independent of IgG opsonization. OmpA binding to FcγRIa prevents γ-chain recruitment and produces a distinct tyrosine phosphorylation pattern from IgG2a-induced phosphorylation. FcγRIa−/− mice are resistant to E. coli K1 meningitis due to accelerated bacterial clearance and increased CR3 expression. COS-1 overexpression of full-length vs. C-terminal truncated FcγRIa; FcγRIa−/− mouse bacterial infection model; adoptive macrophage transfer; co-immunoprecipitation; tyrosine phosphorylation analysis PLoS pathogens High 21124939
2010 Targeting allergen to FcγRI on dendritic cells upregulates TSLP receptor via a signaling pathway requiring FcγRI-associated src-related tyrosine kinases, Syk, and PI3K; inhibition of TSLP receptor upregulation blocks TSLP-mediated Th2 responses, linking FcγRI signaling to a novel Th2 regulatory pathway. Monocyte-derived DC priming with FcγRI-targeting allergen fusion protein (H22-Fel d 1); inhibitors of Fc receptor signaling (src kinases, Syk, PI3K); TSLP receptor flow cytometry; T cell cytokine analysis The Journal of allergy and clinical immunology Medium 20109752
2016 LILRB4 co-ligation with FcγRI causes Tyr dephosphorylation of key clathrin-mediated endocytosis pathway components—including the FcR common γ-chain, Syk, clathrin, Cbl, HRS, TRIM21, and HSP70—and suppresses FcR-dependent uptake of antibody-opsonized bacterial particles, indicating LILRB4 regulates FcγRI-dependent phagocytosis/endocytosis via Tyr dephosphorylation. Antibody ligation of FcγRI ± LILRB4 on THP-1 cells; anti-pTyr immunoprecipitation; mass spectrometry peptide sequencing; Ingenuity Pathway Analysis; bacterial phagocytosis assay Scientific reports High 27725776
2018 Cytokine-induced 'inside-out' signaling enhances FcγRI clustering (nanoscale reorganization) dependent on an intact actin cytoskeleton and on PP1 phosphatase activity (PP1 inhibition reduces inside-out signaling without affecting FcγRI phosphorylation itself); IL-3, TNFα, and IFNγ all stimulate this clustering and enhance ADCC of CD20+ tumor cells by neutrophils. Super-resolution microscopy (STORM) of FcγRI clustering; pharmacological inhibition of PP1; actin cytoskeleton disruption; ADCC assay with neutrophils Science signaling High 30042128
2018 FcγRI/CD64 promotes immune inflammation via activation of NF-κB signaling, which in turn drives NLRP3 inflammasome formation and IL-1β/IL-18 release; FcγRI expression in Ba/F3 cells induces this pathway, and silencing FcγRI in THP-1 macrophages reverses it. FcγRI overexpression in Ba/F3 cells; FcγRI siRNA knockdown in THP-1 macrophages; NF-κB inhibitor (PDTC); western blotting for NLRP3 components; ELISA for IL-1β and IL-18 Life sciences Medium 29920250
2019 FcγRI is expressed in a subpopulation of joint sensory neurons; IgG immune complex crosslinking of FcγRI directly activates the somata and peripheral terminals of these neurons to evoke acute joint hypernociception without joint inflammation. Conditional deletion of Fcgr1 in sensory neurons attenuated arthritis pain and joint sensory neuron hyperactivity without altering joint inflammation. Global and sensory-neuron-specific Fcgr1 conditional knockout mice; ex vivo electrophysiology of joint sensory neurons; behavioral pain assays; inflammatory arthritis models; IgG-IC injection The Journal of clinical investigation High 31211699
2001 Exogenous antigen targeted to FcγRI (CD64) on myeloid cells (THP-1) is internalized and processed for presentation on MHC class I molecules, enabling CTL-mediated lysis; blocking either FcγRI or MHC class I abrogates lysis, demonstrating FcγRI-mediated cross-presentation (MHC I) pathway. FcγRI-targeted PSA fusion protein (FPH22.PSA) on THP-1 cells; CTL cytotoxicity assay; receptor-blocking with anti-FcγRI and anti-MHC class I antibodies Journal of immunological methods Medium 11223078
2004 FcγRI-mediated cross-presentation via MHC class I is enhanced by CpG ODN co-stimulation; hFcγRI transgenic DC show increased MHC class I presentation of FcγRI-targeted antigens (ovalbumin via CD64 mAb fusion) upon CpG addition compared to non-transgenic DC. hFcγRI transgenic and non-transgenic DC; antigen-CD64 mAb fusion protein targeting; CpG ODN co-stimulation; MHC class I presentation assay with OVA-specific CD8+ T cells International immunology Medium 15192052
2004 FcγRI (CD64) and FcγRIIB on dendritic cells and macrophages both mediate accelerated antigen presentation (T cell proliferation, IgG production) via immune complex uptake; DC lacking FcγRIIB show reduced IC-uptake and decreased T-cell stimulation, while DC expressing only FcγRIIB (FcR γ-chain deficient) outperform FcγR-null DC, revealing positive regulation of antigen presentation by FcγRIIB alongside FcγRI/III. FcγRIIB KO and FcR γ-chain KO bone marrow-derived DCs; antigen IC uptake assay; T cell proliferation assay; adoptive DC transfer; serum IgG measurement Cellular immunology Medium 14643301
1998 FcγRIa-γ-chain complexes require an intact γ-chain ITAM to trigger phagocytosis of S. aureus and ADCC of erythrocytes in IIA1.6 cells; both γ-chain ITAM and FcγRIIa ITAM can direct these functions when coupled to the FcγRIa extracellular domain. FcγRIa-γ-chain complex reconstitution in IIA1.6 cells; ITAM mutant γ-chain; phagocytosis of S. aureus; ADCC assay with erythrocytes Clinical and experimental immunology Medium 9737671
2004 FcγRIIA interacts more readily with Syk than does FcγRI/γ-chain chimera, contributing to greater phagocytic efficiency of FcγRIIA; individual Src-related tyrosine kinases (Hck, Lyn) differentially influence phagocytosis efficiency and Syk interaction for FcγRI/γ versus FcγRIIA. Transfection of FcγRIIA and FcγRI-gamma-gamma chimera in COS-1 cells; co-immunoprecipitation with Syk, Hck, Lyn; phagocytosis assay Journal of leukocyte biology Medium 15136586
2023 Conditional knockout of Fcgr1 in rat DRG neurons significantly alleviates neuropathic pain after sciatic nerve injury; CRP (elevated in DRG after nerve injury) activates neuronal FcγRI-related signals to evoke pain, and microinjection of naive IgG into DRG suppresses FcγRI activation and alleviates pain, establishing a CRP/FcγRI positive-feedback proinflammatory signaling loop in sensory neurons. Fcgr1 conditional knockout in rat DRG neurons; CRP microinjection into DRG; naive IgG microinjection; behavioral pain assays; signaling analysis in primary neurons Advanced science Medium 36727833
2015 Crystal/structural studies of human FcγRI in complex with IgG-Fc revealed the molecular basis for high-affinity binding, including a potential receptor-glycan interaction as a contributor to affinity differences among FcγRs. Structural determination (crystallography) of FcγRI–IgG-Fc complex with review of structural data Immunological reviews Medium 26497521
2012 CD64 (FcγRI) modulates the inhibitory activity of infliximab: cells expressing CD64 capture infliximab-TNF complexes via the Fc domain, activating CD64 and producing distinct phospho-tyrosine signals; blocking the Fc portion or using Fab fragments of infliximab improves its TNF-neutralizing efficacy. IFN-γ-induced CD64 upregulation correlates with loss of infliximab efficacy, and CD64 knockdown (siRNA) or downregulation (PMA) restores it. siRNA knockdown of CD64 in THP-1 and PBMCs; Fc-blocking antibody fragments; immunoprecipitation; western blotting for phospho-tyrosine; RT-PCR; immunofluorescence PloS one High 22937039
2022 FCGR1A variants affect CD64 functions: promoter SNV rs1848781 alters promoter activity and CD64 expression levels; intronic indel rs587598788 associates with CD64 expression levels; non-synonymous SNV rs1050204 (p.D324N) significantly affects CD64-mediated phagocytosis, degranulation, and pro-inflammatory cytokine production. Promoter reporter assay; genotype-phenotype analysis; phagocytosis assay; degranulation assay; cytokine measurement in cells with different FCGR1A genotypes Frontiers in immunology Medium 35371020
2025 Guselkumab (but not risankizumab) binds CD64 on IFNγ-primed monocytes via its Fc domain, enabling simultaneous capture of IL-23 secreted from CD64+ IL-23-producing inflammatory monocytes; this Fc/CD64-dependent mechanism mediates IL-23 internalization into low-pH compartments and enhances potency of IL-23 neutralization in a CD64+ cell co-culture system. Flow cytometry binding assays; live-cell confocal imaging of IL-23 internalization; co-culture of CD64+ THP-1 IL-23-producing cells with IL-23-responsive reporter cells; Fc-mutant antibody comparison Frontiers in immunology Medium 40145093

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 FcgammaRI (CD64) contributes substantially to severity of arthritis, hypersensitivity responses, and protection from bacterial infection. Immunity 223 11911824
2008 Lymphoma depletion during CD20 immunotherapy in mice is mediated by macrophage FcgammaRI, FcgammaRIII, and FcgammaRIV. Blood 173 18495955
1996 Type I (CD64) and type II (CD32) Fc gamma receptor-mediated phagocytosis by human blood dendritic cells. Journal of immunology (Baltimore, Md. : 1950) 162 8752900
2002 FcgammaRI-deficient mice show multiple alterations to inflammatory and immune responses. Immunity 155 11911823
2010 Neutrophil CD64 expression as marker of bacterial infection: a systematic review and meta-analysis. The Journal of infection 130 20206205
2011 Functional characteristics of the high affinity IgG receptor, FcγRI. Journal of immunology (Baltimore, Md. : 1950) 128 21325219
2009 Neutrophil CD64: a diagnostic marker for infection and sepsis. Clinical chemistry and laboratory medicine 126 19642859
1997 Clinical experience with CD64-directed immunotherapy. An overview. Cancer immunology, immunotherapy : CII 114 9435876
2012 Neutrophil CD64 expression as a biomarker in the early diagnosis of bacterial infection: a meta-analysis. International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases 105 22940278
2006 Differential enhancement of dengue virus immune complex infectivity mediated by signaling-competent and signaling-incompetent human Fcgamma RIA (CD64) or FcgammaRIIA (CD32). Journal of virology 103 17005690
2004 Activation of human mast cells by aggregated IgG through FcgammaRI: additive effects of C3a. Clinical immunology (Orlando, Fla.) 91 15003814
2015 Neutrophil CD64 expression as a diagnostic marker for sepsis in adult patients: a meta-analysis. Critical care (London, England) 89 26059345
2001 Increased distribution and expression of CD64 on blood polymorphonuclear cells from patients with the systemic inflammatory response syndrome (SIRS). Clinical and experimental immunology 87 11529918
2010 Monocyte surface expression of Fcgamma receptor RI (CD64), a biomarker reflecting type-I interferon levels in systemic lupus erythematosus. Arthritis research & therapy 78 20478071
1996 Adaptation to eccentric exercise: effect on CD64 and CD11b/CD18 expression. Journal of applied physiology (Bethesda, Md. : 1985) 75 8847330
2003 Accelerated antigen presentation and elicitation of humoral response in vivo by FcgammaRIIB- and FcgammaRI/III-mediated immune complex uptake. Cellular immunology 73 14643301
1999 The FcgammaRIa (CD64) ligand binding chain triggers major histocompatibility complex class II antigen presentation independently of its associated FcR gamma-chain. Blood 72 10397749
2000 Therapeutic efficacy of FcgammaRI/CD64-directed bispecific antibodies in B-cell lymphoma. Blood 59 11071653
2008 Evaluation of neutrophil CD64 expression and procalcitonin as useful markers in early diagnosis of sepsis. International journal of immunopathology and pharmacology 55 18336730
2019 The Impact of FcγRI Binding on Immuno-PET. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 54 30733320
2007 Hematological indices, inflammatory markers and neutrophil CD64 expression: comparative trends during experimental human endotoxemia. Journal of endotoxin research 52 17621550
1998 The second and third extracellular domains of FcgammaRI (CD64) confer the unique high affinity binding of IgG2a. Molecular immunology 52 9881694
2019 Neuronal FcγRI mediates acute and chronic joint pain. The Journal of clinical investigation 51 31211699
2015 The many faces of FcγRI: implications for therapeutic antibody function. Immunological reviews 48 26497519
2010 The novel applications of the quantitative analysis of neutrophil cell surface FcgammaRI (CD64) to the diagnosis of infectious and inflammatory diseases. Current opinion in infectious diseases 44 20407370
2009 Expression of the high-affinity IgG receptor FcRI (CD64) in patients with inflammatory bowel disease: a new biomarker for gastroenterologic diagnostics. The American journal of gastroenterology 43 19098857
2009 Leukocyte Ig-like receptor B4 (LILRB4) is a potent inhibitor of FcgammaRI-mediated monocyte activation via dephosphorylation of multiple kinases. The Journal of biological chemistry 43 19833736
2001 Exogenous antigen targeted to FcgammaRI on myeloid cells is presented in association with MHC class I. Journal of immunological methods 43 11223078
2018 Immunophenotyping of Monocytes During Human Sepsis Shows Impairment in Antigen Presentation: A Shift Toward Nonclassical Differentiation and Upregulation of FCγRi-Receptor. Shock (Augusta, Ga.) 41 29668526
2012 Fc gamma receptor CD64 modulates the inhibitory activity of infliximab. PloS one 41 22937039
2024 An engineered α1β1 integrin-mediated FcγRI signaling component to control enhanced CAR macrophage activation and phagocytosis. Journal of controlled release : official journal of the Controlled Release Society 40 39617174
2020 Role of the interferons in CD64 and CD169 expressions in whole blood: Relevance in the balance between viral- or bacterial-oriented immune responses. Immunity, inflammation and disease 40 32031762
2015 Structural mechanism of high affinity FcγRI recognition of immunoglobulin G. Immunological reviews 36 26497521
2010 Fcγ receptor I alpha chain (CD64) expression in macrophages is critical for the onset of meningitis by Escherichia coli K1. PLoS pathogens 36 21124939
2000 Production of macrophage-activated killer cells for targeting of glioblastoma cells with bispecific antibody to FcgammaRI and the epidermal growth factor receptor. Cancer immunology, immunotherapy : CII 36 11092616
2023 Protection of cell therapeutics from antibody-mediated killing by CD64 overexpression. Nature biotechnology 34 36593395
2011 Evaluation of adhesion molecules CD64, CD11b and CD62L in neutrophils and monocytes of peripheral blood for early diagnosis of neonatal infection. World journal of pediatrics : WJP 34 21874613
2018 FcγRI (CD64) contributes to the severity of immune inflammation through regulating NF-κB/NLRP3 inflammasome pathway. Life sciences 33 29920250
2005 Neutrophil CD64 expression in Behçet's disease. The Journal of rheumatology 33 15868620
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