Affinage

CX3CR1

CX3C chemokine receptor 1 · UniProt P49238

Length
355 aa
Mass
40.4 kDa
Annotated
2026-06-09
100 papers in source corpus 27 papers cited in narrative 27 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CX3CR1 is a seven-transmembrane G protein-coupled receptor for the chemokine fractalkine (CX3CL1) that couples leukocyte and microglial biology to chemotaxis, adhesion, and cell survival (PMID:9390561). It mediates two functionally separable outputs: pertussis toxin-independent leukocyte adhesion that requires the chemokine domain presented atop the fractalkine mucin stalk, and pertussis toxin-sensitive, G protein-dependent migration (PMID:9390561). Cryo-EM structures of the CX3CR1–Gi1 complex in ligand-free and CX3CL1-bound states show a comparatively small helix VI movement upon activation, stabilized by three bound cholesterol molecules essential for conformation and signal transduction (PMID:35767622). Downstream of CX3CL1, the receptor activates PI3K–AKT and ERK signaling to deliver pro-survival signals: it protects neurons from gp120 neurotoxicity through PI3K–Akt and NF-κB (PMID:10869418), and sustains non-classical monocyte survival—a function abolished by the M280 loss-of-function variant, which impairs AKT/ERK activation without altering surface receptor levels (PMID:18971423, PMID:29415879). In microglia, CX3CR1 supports NRF2 signaling, migration and phagocytosis and restrains a premature aging transcriptome (PMID:30769286, PMID:31792059), and it serves as a direct binding receptor for extracellular Tau—competing with CX3CL1 and driving microglial Tau internalization, with phospho-S396 Tau binding more weakly (PMID:28810892). Beyond immune and neural roles, CX3CR1 is expressed on pancreatic β cells where it potentiates glucose-stimulated insulin secretion via intracellular Ca²⁺ (PMID:23582329), and functions as an entry/infection receptor for respiratory syncytial virus in airway epithelium in vitro and in vivo (PMID:31726465, PMID:34037420). A CX3CR1 missense variant in Crohn's disease patients impairs Syk-dependent antifungal responses of mononuclear phagocytes (PMID:29326275).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 1997 High

    Established the receptor identity and the dual-output logic of fractalkine signaling, distinguishing G protein-independent adhesion from G protein-dependent migration.

    Evidence expression cloning with adhesion/migration assays and pertussis toxin inhibition across leukocytes including NK cells

    PMID:9390561

    Open questions at the time
    • Structural basis for how the chemokine/mucin architecture drives adhesion was not resolved
    • In vivo relevance of the two outputs not addressed
  2. 1997 Medium

    Tested whether this orphan receptor (V28) could act as a viral co-receptor, broadening its functional range beyond chemotaxis.

    Evidence transient transfection of feline CCC cells supporting CD4-independent HIV-2 entry with sCD4

    PMID:9143311

    Open questions at the time
    • Single transfection/infection assay without binding-domain mapping
    • No follow-up establishing physiological HIV co-receptor role
  3. 2000 High

    Identified the downstream survival pathway by showing CX3CL1 engages PI3K-Akt and NF-κB to protect neurons.

    Evidence primary hippocampal neurons with antibody block, PI3K inhibition, and Akt/NF-κB readouts under gp120 neurotoxicity

    PMID:10869418

    Open questions at the time
    • Endogenous neuronal CX3CR1 contribution in vivo not defined
    • Link between Akt and NF-κB activation not mechanistically dissected
  4. 2002 Medium

    Defined cytokine control of receptor abundance, showing TGF-β1 transcriptionally upregulates CX3CR1 in microglia via Smad elements.

    Evidence primary rat microglia with binding assays, ERK phosphorylation, mRNA stability, and promoter analysis

    PMID:12446007

    Open questions at the time
    • Direct Smad occupancy of the promoter not demonstrated
    • Functional consequence of blunted ERK signaling unclear
  5. 2003 Medium

    Mapped the transcriptional architecture of CX3CR1 (three human promoters/exons) and established mouse-human divergence.

    Evidence genomic cloning, promoter-luciferase reporters, comparative genomics

    PMID:12551893

    Open questions at the time
    • Cell-type-specific promoter usage not assigned
    • Trans-acting factors for the regulatory elements not identified
  6. 2003 High

    Showed cytokine-specific regulation of NK-cell CX3CR1, with IL-15 suppressing and IL-2 increasing receptor expression and chemotactic function.

    Evidence primary mouse NK cells, in vivo IL-15 injection, RT-PCR, flow cytometry, chemotaxis assays

    PMID:12881312

    Open questions at the time
    • Transcriptional mechanism of IL-15 suppression undefined
    • Physiological context where IL-15 modulates NK trafficking not established
  7. 2004 Medium

    Extended IL-15 regulation to human NK cells, linking surface receptor loss to diminished calcium flux and chemotaxis.

    Evidence human CD56+ NK cells, flow cytometry, calcium flux, and chemotaxis assays with CCR5/CXCR4 specificity controls

    PMID:15598425

    Open questions at the time
    • Single lab
    • Mechanism of selective receptor downregulation not resolved
  8. 2008 High

    Established that CX3CR1 delivers a pro-survival signal to non-classical monocytes, with downstream consequences for atherogenesis.

    Evidence CX3CR1/CX3CL1 knockout mice, Bcl2 transgene rescue, in vitro survival assays, atherosclerosis model

    PMID:18971423

    Open questions at the time
    • Signaling intermediates linking receptor to survival not detailed here
    • Whether survival is the sole atherogenic mechanism not excluded
  9. 2011 Medium

    Generalized the survival function to DC and monocyte/macrophage development, distinguishing survival promotion from homing.

    Evidence competitive adoptive transfer with direct organ-injection controls and flow cytometry

    PMID:21425158

    Open questions at the time
    • Molecular survival pathway in precursors not defined
    • Ligand source supporting precursor survival unknown
  10. 2013 High

    Revealed a non-immune endocrine role, showing CX3CR1 potentiates β-cell insulin secretion via intracellular Ca²⁺.

    Evidence CX3CR1 KO mice, isolated mouse and human islet secretion assays, glucose tolerance tests, Ca²⁺ imaging, gene expression profiling

    PMID:23582329

    Open questions at the time
    • Coupling between Ca²⁺ elevation and secretory machinery not detailed
    • G protein dependence of the islet effect not specified
  11. 2017 High

    Identified CX3CR1 as a direct extracellular Tau receptor mediating microglial Tau uptake, with phosphorylation modulating affinity.

    Evidence affinity chromatography, CX3CL1-Tau competition binding, microglial uptake assays, in vivo stereotaxic Tau clearance in KO mice

    PMID:28810892

    Open questions at the time
    • Tau binding site on the receptor not mapped
    • Whether Tau triggers canonical signaling or only internalization unclear
  12. 2018 High

    Tied a human loss-of-function variant (M280) to defective monocyte survival via impaired AKT/ERK, with surface expression preserved.

    Evidence primary monocytes from genotyped human donors, serum-starvation survival assays, AKT/ERK Western blots, flow cytometry

    PMID:29415879

    Open questions at the time
    • How M280 selectively impairs G protein/kinase coupling not structurally defined
    • Disease consequences of impaired survival not directly tested here
  13. 2018 Medium

    Linked CX3CR1 to vascular disease through macrophage polarization, showing deficiency protects against hypoxic pulmonary hypertension.

    Evidence CX3CR1-/- mice in hypoxic PH model with macrophage polarization, conditioned-media SMC proliferation, and pharmacological inhibition

    PMID:28125278

    Open questions at the time
    • Direct receptor signaling driving polarization not isolated
    • CX3CL1 source in the lung niche not defined
  14. 2019 Medium

    Connected CX3CR1 to microglial homeostasis by showing it sustains NRF2 signaling, migration, and phagocytosis.

    Evidence primary Cx3cr1-/- microglia, RT-PCR for Nrf2 targets, migration/phagocytosis assays, in vivo sulforaphane in a tauopathy model

    PMID:30769286

    Open questions at the time
    • Mechanistic link from receptor to NRF2 induction unknown
    • Single lab
  15. 2019 Medium

    Showed CX3CR1 normally restrains a premature microglial aging transcriptome without major chromatin remodeling.

    Evidence RNA-seq and ATAC-seq of Cx3cr1-/- vs WT microglia with morphological analysis

    PMID:31792059

    Open questions at the time
    • Transcriptional regulators downstream of CX3CR1 not identified
    • Functional consequence of the aging signature in vivo not tested
  16. 2019 Medium

    Identified CX3CR1 as an RSV receptor in human pediatric airway epithelium.

    Evidence in situ hybridization, IHC, and CX3CR1-blocking with viral load readout in primary differentiated airway cultures

    PMID:31726465

    Open questions at the time
    • Receptor-virus binding interface not mapped in this study
    • Antibody blocking alone without genetic confirmation
  17. 2021 High

    Confirmed CX3CR1 as an RSV receptor in vivo and defined the G-protein CX3CR1 binding site as required for infection.

    Evidence recombinant RSV with G-protein mutations, antibody block, and morpholino knockdown of CX3CR1 in cotton rats

    PMID:34037420

    Open questions at the time
    • Post-attachment entry steps mediated by CX3CR1 not defined
    • Relevance to human in vivo infection not directly shown
  18. 2022 High

    Provided the structural mechanism of activation, showing a small helix VI shift stabilized by three cholesterol molecules.

    Evidence cryo-EM of CX3CR1-Gi1 in ligand-free and CX3CL1-bound states with functional validation

    PMID:35767622

    Open questions at the time
    • Structural basis of adhesion vs migration outputs not resolved
    • How M280 or Tau binding alter the structure not addressed
  19. 2018 High

    Linked a human CX3CR1 variant to impaired Syk-dependent antifungal immunity and colitis, establishing a Crohn's disease connection.

    Evidence CX3CR1+ MNP genetic ablation in mice, Syk inhibition, microbiome analysis, human genetic association with functional validation

    PMID:29326275

    Open questions at the time
    • Direct CX3CR1 signaling to Syk-coupled antifungal receptors not mapped
    • Causal chain from receptor variant to fungal dysbiosis incompletely defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single receptor with a structurally subtle activation mechanism partitions among adhesion, chemotaxis, survival signaling, Tau/viral binding, and Ca²⁺-coupled secretion across diverse cell types remains unresolved.
  • No unified model linking ligand/cholesterol-stabilized conformation to divergent outputs
  • Binding interfaces for non-chemokine ligands (Tau, RSV G protein) not structurally co-defined
  • Cell-type-specific effector coupling not systematically mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0001618 virus receptor activity 2 GO:0060089 molecular transducer activity 2 GO:0098631 cell adhesion mediator activity 1
Localization
GO:0005886 plasma membrane 3
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 3 R-HSA-1500931 Cell-Cell communication 1
Partners
CX3CL1GNAI1MAPT

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 CX3CR1 was identified as a high-affinity seven-transmembrane G protein-coupled receptor for fractalkine (CX3CL1). It mediates both leukocyte adhesion (independent of pertussis toxin-sensitive G protein signaling and other adhesion molecules, but requiring the chemokine domain atop mucin stalk architecture) and migration (requiring pertussis toxin-sensitive G protein signaling). NK cells predominantly express CX3CR1 and respond to fractalkine in both functions. Receptor identification by expression cloning; functional adhesion and migration assays; pertussis toxin inhibition experiments Cell High 9390561
1997 The orphan G protein-coupled receptor V28 (now known as CX3CR1) shows high sequence similarity to chemokine receptors and can support CD4-independent HIV-2 (ROD/B) entry into feline CCC cells in the presence of sCD4, indicating it can function as an HIV co-receptor. Transient transfection of CCC cells with V28 followed by HIV-2 infection assay Virology Medium 9143311
2000 Hippocampal neurons express CX3CR1, and receptor activation by soluble fractalkine induces Akt phosphorylation and nuclear translocation of NF-κB, protecting neurons from HIV-1 gp120-induced neurotoxicity. Phosphatidylinositol 3-kinase inhibitors blocked both Akt activation and neuroprotection, establishing the PI3K-Akt pathway as the downstream mechanism. Primary hippocampal neuron cultures, anti-CX3CR1 antibody blocking, PI3K inhibitors, Akt phosphorylation assays, NF-κB nuclear translocation assay, cell viability assay Proceedings of the National Academy of Sciences of the United States of America High 10869418
2002 TGF-β1 increases CX3CR1 mRNA, protein, and 125I-fractalkine binding sites in rat microglia, while blunting fractalkine-stimulated ERK1/2 phosphorylation. The CX3CR1 mRNA half-life was unaltered, and two Smad binding elements were identified in the rat CX3CR1 promoter, suggesting transcriptional upregulation via Smad signaling. Primary rat microglia cultures, Northern/qPCR, 125I-fractalkine binding assay, ERK1/2 phosphorylation by Western blot, mRNA stability assay, promoter analysis Journal of neuroimmunology Medium 12446007
2003 CX3CR1 has three promoters that transcribe three separate exons spliced with a fourth coding exon. Luciferase reporter assays identified positive and negative regulatory elements within these promoters. Mouse CX3CR1 lacks two human promoters and has an additional mouse-specific promoter. Genomic cloning, promoter-luciferase reporter assays, comparative genomics The Journal of biological chemistry Medium 12551893
2003 IL-15 specifically inhibits CX3CR1 protein and mRNA accumulation in mouse NK cells (primary bone marrow-derived), whereas IL-2 increases CX3CR1 expression. In vivo injection of IL-15 decreased steady-state CX3CR1 levels in PBMCs, splenocytes, and bone marrow cells; IL-15 treatment also inhibited CX3CL1-induced chemotaxis. Primary mouse NK cell cultures, in vivo IL-15 injection, flow cytometry, RT-PCR, chemotaxis assays Blood High 12881312
2004 IL-15 decreases surface expression of CX3CR1 on human CD56+ NK cells, resulting in diminished CX3CL1-induced chemotaxis and calcium flux. Long-term IL-15 culture abolished CX3CR1 mRNA and protein. The effect was specific: CCR5 mRNA increased while CXCR4 was unchanged. Human NK cell cultures, flow cytometry, RT-PCR, Western blot, calcium flux assay, chemotaxis assay Cellular immunology Medium 15598425
2008 Absence of CX3CR1 or CX3CL1 results in reduced Gr1low (non-classical) blood monocyte levels. CX3CL1 specifically rescues human monocytes from induced cell death, and introduction of a Bcl2 transgene restored wild-type monocyte levels in CX3CR1-deficient mice, establishing that CX3CR1 provides a pro-survival signal to monocytes. Enforced monocyte survival restored atherogenesis in CX3CR1-deficient mice. CX3CR1 knockout mice, CX3CL1 knockout mice, Bcl2 transgene rescue, in vitro monocyte survival assay with CX3CL1, flow cytometry, atherosclerosis model Blood High 18971423
2013 CX3CR1 is expressed on pancreatic islet β cells, and CX3CR1 knockout mice exhibit defective glucose- and GLP1-stimulated insulin secretion in vivo and in vitro. FKN treatment of wild-type islets increased intracellular Ca2+ and potentiated insulin secretion in mouse and human islets. KO islets showed reduced expression of genes necessary for differentiated β cell function. CX3CR1 KO mice, isolated islet insulin secretion assays, in vivo glucose tolerance tests, Ca2+ imaging, gene expression profiling Cell High 23582329
2017 CX3CR1 directly binds extracellular Tau and triggers its internalization by microglia. Affinity chromatography and competition assays showed Tau competes with CX3CL1 for CX3CR1 binding. Phosphorylation of Tau at S396 reduces its binding affinity for CX3CR1. CX3CR1-deficient mice showed impaired Tau clearance after stereotaxic injection. Affinity chromatography, CX3CL1-Tau competition binding assay, Cy5-Tau uptake in primary microglia cultures from WT and CX3CR1-/- mice, in vivo stereotaxic Cy5-Tau injection Molecular neurodegeneration High 28810892
2018 A missense mutation in CX3CR1 identified in Crohn's disease patients is associated with impaired antifungal responses. CX3CR1+ mononuclear phagocytes express antifungal receptors and activate antifungal responses in a Syk-dependent manner. Genetic ablation of CX3CR1+ MNPs in mice led to changes in gut fungal communities and severe colitis rescued by antifungal treatment. CX3CR1+ MNP genetic ablation mouse model, Syk inhibition assays, antifungal response assays, microbiome analysis, human genetic association with functional validation Science (New York, N.Y.) High 29326275
2019 CX3CR1 deficiency in microglia impairs NRF2 signaling: mRNA levels of Nrf2 and its target genes were significantly decreased in primary microglia from Cx3cr1-/- mice. CX3CR1-deficient microglia also showed impaired cell migration and phagocytosis, phenocopying NRF2-deficient microglia. Sulforaphane (NRF2 inducer) failed to reduce microgliosis in Cx3cr1-/- mice. Primary microglia from Cx3cr1-/- mice, RT-PCR for Nrf2 and target genes, migration assays, phagocytosis assays, in vivo sulforaphane treatment in tauopathy model Redox biology Medium 30769286
2019 Cx3cr1-deficient microglia from 2-month-old mice exhibit a transcriptomic signature consistent with aged (wild-type) microglia, indicating that CX3CR1 signaling normally restrains a premature aging transcriptome. Loss of Cx3cr1 down-regulates a subset of immune-related genes without substantial epigenetic changes in active chromatin markers. RNA-sequencing of Cx3cr1-/- vs. WT microglia at multiple ages, ATAC-seq for chromatin accessibility, immunohistochemistry for microglial morphology Life science alliance Medium 31792059
2019 CX3CR1 is expressed on tendon-resident macrophage-like cells ('tenophages') together with its ligand CX3CL1. Inhibition of CX3CR1 (fractalkine receptor) blocked tendon cell migration in vitro in 3D tendon-like constructs. Transgenic reporter mouse models, 3D tendon constructs with CX3CR1 inhibitor, cell migration assay, immunohistochemistry of human tendon Disease models & mechanisms Low 31744815
2019 CX3CR1+ mononuclear phagocytes expressing LAG-3+ Treg cell-suppressed IL-23 and IL-1β production. The suppression was contact dependent and mediated by LAG-3 engagement of MHC class II on CX3CR1+ macrophages, driving their immunosuppression. In vivo ILC3-colitis model, conditional depletion of CX3CR1+ macrophages, LAG-3 blocking, contact-dependent suppression assays Immunity Medium 30097293
2018 CX3CR1 deficiency in the homozygous M280 variant impairs CX3CL1-induced monocyte survival. CX3CL1 rescues serum starvation-induced cell death in CX3CR1-WT/WT and heterozygous but not CX3CR1-M280/M280 monocytes. The survival mechanism requires AKT and ERK activation, both of which are impaired in M280/M280 monocytes. CX3CR1-M280/M280 does not affect CX3CR1 surface expression or innate immune effector functions. Primary monocytes from genotyped human donors (WT, heterozygous, homozygous M280), serum starvation survival assay, AKT/ERK phosphorylation by Western blot, flow cytometry JCI insight High 29415879
2022 Cryo-electron microscopy structures of CX3CR1-Gi1 complexes in ligand-free and CX3CL1-bound states (2.8 Å and 3.4 Å resolution) revealed key residues governing CX3CL1 recognition. CX3CR1 shows a smaller conformational change in helix VI upon activation than other class A GPCRs, correlated with three cholesterol molecules that play essential roles in conformation stabilization and signaling transduction. Functional assays validated the structural findings. Cryo-EM structure determination, functional signaling assays, cholesterol interaction analysis Science advances High 35767622
2019 CX3CR1 functions as a receptor for respiratory syncytial virus (RSV) in pediatric airway epithelial cells. RSV preferentially infects CX3CR1-positive cells, and blocking CX3CR1/RSV interaction significantly decreased viral load in primary cultures of differentiated pediatric/infant lung epithelial cells. In situ hybridization, immunohistochemistry, CX3CR1-blocking experiments in primary pediatric airway epithelial cell cultures, viral load measurement Pediatric research Medium 31726465
2021 CX3CR1 functions as a receptor for RSV in vivo in cotton rats. RSV mutants with mutations in the CX3CR1 binding site of the G protein failed to grow in cotton rat lungs, and antibody blocking of the CX3CR1 binding site prevented lung infection. Knockdown of cotton rat CX3CR1 by peptide-conjugated morpholino oligomers led to 10-fold reduction in RSV titers. Recombinant RSV with G protein mutations, in vivo intranasal infection in cotton rats, CX3CR1 binding-site blocking antibody, peptide-conjugated morpholino knockdown of CX3CR1 Journal of virology High 34037420
2018 CX3CR1 deficiency protects against hypoxia-induced pulmonary hypertension. The protective effect occurred with a shift from M2 to M1 macrophage polarization, which diminished conditioned media ability to induce pulmonary artery smooth muscle cell proliferation, partially dependent on CX3CL1 secretion. CX3CR1 inhibitor F1 recapitulated effects of genetic deficiency. CX3CR1-/- mice in hypoxic PH model, flow cytometry for monocyte/macrophage subsets, macrophage polarization assays, conditioned media PA-SMC proliferation assay, pharmacological CX3CR1 inhibition American journal of respiratory cell and molecular biology Medium 28125278
2015 TGFβ induces CX3CR1 mRNA expression in T cells in a dose- and time-dependent manner. TH17 polarization or TREG cell generation increased CX3CR1 reporter gene expression. Fewer TH17 cells were obtained from CX3CR1-/- splenocytes under polarizing conditions, and CX3CR1 cell-intrinsically promoted aortic T cell accumulation and IL-17 production in atherosclerosis. Mixed bone marrow chimeras, T cell transfer experiments, TH17/TREG polarization assays, CX3CR1 reporter mice, qPCR for CX3CR1 mRNA Journal of the American Society of Nephrology : JASN Medium 26449606
2011 CX3CR1 expression promotes DC and monocyte/macrophage development under steady-state conditions. Competitive adoptive transfer experiments showed that CX3CR1-deficient precursors had a selective disadvantage in generating DCs and monocytes. Direct intraspleen/intrathymus transfer showed the same competitive advantage, suggesting survival promotion rather than homing is the key mechanism. Competitive adoptive transfer experiments, direct organ injection of precursors, flow cytometric analysis of DC/monocyte output European journal of immunology Medium 21425158
2012 Fractalkine upregulates inflammation through CX3CR1 and the JAK/STAT signaling pathway in pancreatic acinar cells. FKN and CX3CR1 are overexpressed in cerulein-stimulated AR42J cells. AG490 (JAK inhibitor) and FKN-siRNA inhibited JAK/STAT activation and TNF-α expression in vitro and in a severe acute pancreatitis rat model. AR42J cell cerulein stimulation, FKN-siRNA knockdown, AG490 JAK inhibitor, Western blot, RT-PCR, ELISA, immunohistochemistry in rat SAP model Inflammation Medium 22213034
2017 CX3CR1 regulates osteoarthritic chondrocyte proliferation and apoptosis through the Wnt/β-catenin signaling pathway. siRNA knockdown of CX3CR1 in OA chondrocytes activated Wnt/β-catenin (increased nuclear β-catenin, Cyclin D1, MMP-13, phospho-GSK-3β). The Wnt inhibitor XAV-939 abolished the effects of siCX3CR1 on proliferation, apoptosis, and cell cycle. siRNA knockdown of CX3CR1 in OA chondrocytes, XAV-939 Wnt pathway inhibition, Western blot, MTT proliferation assay, flow cytometry for apoptosis/cell cycle Biomedicine & pharmacotherapy Low 29217163
2023 CX3CR1 activation by recombinant fractalkine (r-FKN) promotes hematoma resolution and M2 microglial polarization after germinal matrix hemorrhage via the AMPK/PPARγ signaling pathway. CX3CR1 CRISPR knockout or pharmacological CX3CR1 inhibitor (AZD8797) abolished the protective effects of r-FKN. Selective inhibition of microglial AMPK or PPARγ abrogated the anti-inflammatory effects. Rat GMH model, intranasal r-FKN administration, CX3CR1 CRISPR knockout, AZD8797 pharmacological inhibition, liposome-encapsulated AMPK/PPARγ inhibitors, Western blot, immunofluorescence, hemoglobin assay Stroke Medium 37465997
2020 CX3CR1 directly interacts with Tau and promotes microglial activation, migration, and proliferation. The CX3CR1/Tau interaction influences internalization of extracellular Tau species by microglia. Review/synthesis integrating prior experimental data (affinity chromatography binding data from PMID 28810892 and cell biological assays) Cell & bioscience Low 32944223
2022 CX3CR1-expressing DRG macrophages contribute to arthritis pain. In vitro, CGRP liberates CX3CR1 ligand fractalkine from endothelium, and FKN promotes activation of intracellular kinases, polarization of bone marrow-derived macrophages toward M1-like phenotype, and release of pro-nociceptive IL-6 via CX3CR1 signaling. CX3CR1 GFP/GFP knockout mice in K/BxN serum transfer model, in vitro endothelial CGRP stimulation with FKN measurement, BMDM CX3CR1 signaling kinase assays, macrophage polarization and cytokine ELISA Brain, behavior, and immunity Medium 36115544

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 Identification and molecular characterization of fractalkine receptor CX3CR1, which mediates both leukocyte migration and adhesion. Cell 1178 9390561
2008 CX3CR1 is required for monocyte homeostasis and atherogenesis by promoting cell survival. Blood 396 18971423
2000 Expression of CX3CR1 chemokine receptors on neurons and their role in neuronal survival. Proceedings of the National Academy of Sciences of the United States of America 321 10869418
2013 Neuron-glia crosstalk in health and disease: fractalkine and CX3CR1 take centre stage. Open biology 280 24352739
2018 CX3CR1+ mononuclear phagocytes control immunity to intestinal fungi. Science (New York, N.Y.) 246 29326275
2018 Microglia and Aging: The Role of the TREM2-DAP12 and CX3CL1-CX3CR1 Axes. International journal of molecular sciences 220 29361745
2020 The Impact of the CX3CL1/CX3CR1 Axis in Neurological Disorders. Cells 212 33065974
2014 Modulating neurotoxicity through CX3CL1/CX3CR1 signaling. Frontiers in cellular neuroscience 187 25152714
2017 Absence of CX3CR1 impairs the internalization of Tau by microglia. Molecular neurodegeneration 182 28810892
2018 LAG3+ Regulatory T Cells Restrain Interleukin-23-Producing CX3CR1+ Gut-Resident Macrophages during Group 3 Innate Lymphoid Cell-Driven Colitis. Immunity 170 30097293
2015 Loss of CX3CR1 increases accumulation of inflammatory monocytes and promotes gliomagenesis. Oncotarget 160 25987130
2010 Tickets to the brain: role of CCR2 and CX3CR1 in myeloid cell entry in the CNS. Journal of neuroimmunology 147 20554025
2021 CX3CL1/CX3CR1 signaling targets for the treatment of neurodegenerative diseases. Pharmacology & therapeutics 144 34492237
2014 Fractalkine/CX3CR1 signaling during neuropathic pain. Frontiers in cellular neuroscience 133 24847207
1997 CD4-independent infection by HIV-2 (ROD/B): use of the 7-transmembrane receptors CXCR-4, CCR-3, and V28 for entry. Virology 129 9143311
2013 The fractalkine/CX3CR1 system regulates β cell function and insulin secretion. Cell 122 23582329
2013 Chemokines and atherosclerosis: focus on the CX3CL1/CX3CR1 pathway. Acta pharmacologica Sinica 109 23974513
2008 Decreased expression of the fractalkine receptor CX3CR1 on circulating monocytes as new feature of sepsis-induced immunosuppression. Journal of immunology (Baltimore, Md. : 1950) 105 18424766
2017 Roles for the CX3CL1/CX3CR1 and CCL2/CCR2 Chemokine Systems in Hypoxic Pulmonary Hypertension. American journal of respiratory cell and molecular biology 99 28125278
2019 Cx3CR1 Expression Identifies Distinct Macrophage Populations That Contribute Differentially to Inflammation and Repair. ImmunoHorizons 94 31356156
2010 Fractalkine/CX3CR1: why a single chemokine-receptor duo bears a major and unique therapeutic potential. Expert opinion on therapeutic targets 93 20055718
2002 Up-regulated expression of fractalkine and its receptor CX3CR1 during liver injury in humans. Journal of hepatology 92 12076860
2019 Targeting Microglia Using Cx3cr1-Cre Lines: Revisiting the Specificity. eNeuro 91 31201215
2009 Expression of fractalkine receptor CX3CR1 on cochlear macrophages influences survival of hair cells following ototoxic injury. Journal of the Association for Research in Otolaryngology : JARO 85 19936834
2002 TGF-beta1 upregulates CX3CR1 expression and inhibits fractalkine-stimulated signaling in rat microglia. Journal of neuroimmunology 85 12446007
2002 Expression of the fractalkine receptor (CX3CR1) in human kidney diseases. Kidney international 83 12110009
2020 Lysophosphatidic Acid-Mediated GPR35 Signaling in CX3CR1+ Macrophages Regulates Intestinal Homeostasis. Cell reports 82 32755573
2010 Role of CX3CR1/CX3CL1 axis in primary and secondary involvement of the nervous system by cancer. Journal of neuroimmunology 81 20630606
2019 Cx3cr1-deficient microglia exhibit a premature aging transcriptome. Life science alliance 78 31792059
2020 Interaction of Tau with the chemokine receptor, CX3CR1 and its effect on microglial activation, migration and proliferation. Cell & bioscience 77 32944223
2019 CX3CL1-CX3CR1 interaction mediates macrophage-mesothelial cross talk and promotes peritoneal fibrosis. Kidney international 75 30948201
1995 The orphan G-protein-coupled receptor-encoding gene V28 is closely related to genes for chemokine receptors and is expressed in lymphoid and neural tissues. Gene 74 7590284
2014 Microglia and their CX3CR1 signaling are involved in hippocampal- but not olfactory bulb-related memory and neurogenesis. Brain, behavior, and immunity 73 24933434
2003 CX3CL1 and CX3CR1 expression in human brain tissue: noninflammatory control versus multiple sclerosis. Journal of neuropathology and experimental neurology 70 14533779
2005 Up regulated expression of fractalkine/CX3CL1 and CX3CR1 in patients with systemic sclerosis. Annals of the rheumatic diseases 69 15608300
2004 Expression of fractalkine and its receptor, CX3CR1, in atopic dermatitis: possible contribution to skin inflammation. The Journal of allergy and clinical immunology 69 15131578
2010 CX3CR1/CX3CL1 axis negatively controls glioma cell invasion and is modulated by transforming growth factor-β1. Neuro-oncology 68 20511186
2011 Fractalkine/CX3CR1 signalling in chronic pain and inflammation. Current pharmaceutical biotechnology 66 21466443
2008 Polymorphism in the microglial cell-mobilizing CX3CR1 gene is associated with survival in patients with glioblastoma. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 64 19001328
2007 Defective antitumor responses in CX3CR1-deficient mice. International journal of cancer 64 17372897
2005 Detection of CX3CR1 single nucleotide polymorphism and expression on archived eyes with age-related macular degeneration. Histology and histopathology 64 15944936
2014 The chemokine CX3CL1 (fractalkine) and its receptor CX3CR1: occurrence and potential role in osteoarthritis. Archivum immunologiae et therapiae experimentalis 61 24556958
2014 CX3CR1 is a modifying gene of survival and progression in amyotrophic lateral sclerosis. PloS one 61 24806473
2019 CX3CR1-deficient microglia shows impaired signalling of the transcription factor NRF2: Implications in tauopathies. Redox biology 59 30769286
2016 CX3CL1/CX3CR1 in Alzheimer's Disease: A Target for Neuroprotection. BioMed research international 59 27429982
2020 Inflammescent CX3CR1+CD57+CD8+ T cells are generated and expanded by IL-15. JCI insight 53 32369455
2016 Up-regulated fractalkine (FKN) and its receptor CX3CR1 are involved in fructose-induced neuroinflammation: Suppression by curcumin. Brain, behavior, and immunity 52 26765996
2020 Dissecting the phenotypic and functional heterogeneity of mouse inflammatory osteoclasts by the expression of Cx3cr1. eLife 51 32400390
2019 Crosstalk between the CX3CL1/CX3CR1 Axis and Inflammatory Signaling Pathways in Tissue Injury. Current protein & peptide science 51 30843484
2015 CX3CR1 is dysregulated in blood and brain from schizophrenia patients. Schizophrenia research 51 26285829
2014 Differential expression of the fractalkine chemokine receptor (CX3CR1) in human monocytes during differentiation. Cellular & molecular immunology 51 25502213
2019 CX3CR1 as a respiratory syncytial virus receptor in pediatric human lung. Pediatric research 49 31726465
2016 Therapeutic intervention of inflammatory/immune diseases by inhibition of the fractalkine (CX3CL1)-CX3CR1 pathway. Inflammation and regeneration 48 29259682
2011 Fractalkine and its receptor, CX3CR1, promote hypertensive interstitial fibrosis in the kidney. Hypertension research : official journal of the Japanese Society of Hypertension 47 21451526
2022 Activation of the human chemokine receptor CX3CR1 regulated by cholesterol. Science advances 46 35767622
2019 Tenophages: a novel macrophage-like tendon cell population expressing CX3CL1 and CX3CR1. Disease models & mechanisms 44 31744815
2018 The Role of the Microglial Cx3cr1 Pathway in the Postnatal Maturation of Retinal Photoreceptors. The Journal of neuroscience : the official journal of the Society for Neuroscience 44 29669747
2017 CX3CL1/CX3CR1 Axis, as the Therapeutic Potential in Renal Diseases: Friend or Foe? Current gene therapy 44 29446734
2002 Fractalkine expression and the recruitment of CX3CR1+ cells in the prolonged mesangial proliferative glomerulonephritis. Kidney international 44 12028445
2021 Regulation and function of CX3CR1 and its ligand CX3CL1 in kidney disease. Cell and tissue research 42 34009468
2020 Revising CX3CR1 Expression on Murine Classical and Non-classical Monocytes. Frontiers in immunology 42 32582197
2013 Fractalkine (CX3CL1) and its receptor CX3CR1 may contribute to increased angiogenesis in diabetic placenta. Mediators of inflammation 42 23956503
2012 Ccl2, Cx3cr1 and Ccl2/Cx3cr1 chemokine deficiencies are not sufficient to cause age-related retinal degeneration. Experimental eye research 41 23232206
2024 CX3CL1 (Fractalkine)-CX3CR1 Axis in Inflammation-Induced Angiogenesis and Tumorigenesis. International journal of molecular sciences 40 38731899
2004 Fractalkine and its receptor, CX3CR1, upregulation in streptozotocin-induced diabetic kidneys. Nephron. Experimental nephrology 40 15153757
2022 CX3CR1 Acts as a Protective Biomarker in the Tumor Microenvironment of Colorectal Cancer. Frontiers in immunology 39 35140706
2020 Role of CX3CR1 signaling in malignant transformation of gliomas. Neuro-oncology 39 32236410
2020 Microglial CX3CR1 production increases in Alzheimer's disease and is regulated by noradrenaline. Glia 39 32662924
2017 Gas6 Promotes Inflammatory (CCR2hiCX3CR1lo) Monocyte Recruitment in Venous Thrombosis. Arteriosclerosis, thrombosis, and vascular biology 39 28450294
2023 Fractalkine/CX3CR1-Dependent Modulation of Synaptic and Network Plasticity in Health and Disease. Neural plasticity 38 36644710
2003 IL-15 and IL-2 oppositely regulate expression of the chemokine receptor CX3CR1. Blood 37 12881312
2022 Dorsal root ganglia CX3CR1 expressing monocytes/macrophages contribute to arthritis pain. Brain, behavior, and immunity 35 36115544
2023 Fractalkine Enhances Hematoma Resolution and Improves Neurological Function via CX3CR1/AMPK/PPARγ Pathway After GMH. Stroke 33 37465997
2017 CX3CR1 knockout aggravates Coxsackievirus B3-induced myocarditis. PloS one 33 28800592
2006 Association study between the CX3CR1 gene and asthma. Genes and immunity 33 17082760
2014 CX3CL1/CX3CR1 and CCL2/CCR2 chemokine/chemokine receptor complex in patients with AMD. PloS one 31 25503251
2021 Dynamic role of macrophage CX3CR1 expression in inflammatory bowel disease. Immunology letters 30 33582183
2019 Role of CX3CL1/CX3CR1 Signaling Axis Activity in Osteoporosis. Mediators of inflammation 29 31780870
2015 Metabolic Effects of CX3CR1 Deficiency in Diet-Induced Obese Mice. PloS one 29 26393344
2015 T Cell CX3CR1 Mediates Excess Atherosclerotic Inflammation in Renal Impairment. Journal of the American Society of Nephrology : JASN 29 26449606
2015 Expression pattern of Ccr2 and Cx3cr1 in inherited retinal degeneration. Journal of neuroinflammation 29 26458944
2012 Fractalkine upregulates inflammation through CX3CR1 and the Jak-Stat pathway in severe acute pancreatitis rat model. Inflammation 29 22213034
2010 Relevance of the CX3CL1/fractalkine-CX3CR1 pathway in vasculitis and vasculopathy. Translational research : the journal of laboratory and clinical medicine 29 20004358
2022 Structure and Function of Ligand CX3CL1 and its Receptor CX3CR1 in Cancer. Current medicinal chemistry 28 35770395
2015 Neuronal Cx3cr1 Deficiency Protects against Amyloid β-Induced Neurotoxicity. PloS one 28 26038823
2011 Chemokine receptor CX3CR1 promotes dendritic cell development under steady-state conditions. European journal of immunology 28 21425158
2008 Characterisation of fractalkine/CX3CL1 and fractalkine receptor (CX3CR1) expression in abdominal aortic aneurysm disease. European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery 28 18296082
2017 The Multifaceted Personality of Intestinal CX3CR1+ Macrophages. Trends in immunology 27 28844811
2004 IL-15 alters expression and function of the chemokine receptor CX3CR1 in human NK cells. Cellular immunology 27 15598425
2021 CX3CR1 Is a Receptor for Human Respiratory Syncytial Virus in Cotton Rats. Journal of virology 26 34037420
2018 The homozygous CX3CR1-M280 mutation impairs human monocyte survival. JCI insight 26 29415879
2015 Chemokine CX3CL1 and its receptor CX3CR1 are associated with human atherosclerotic lesion volnerability. Thrombosis research 26 25845619
2017 CX3CR1 regulates osteoarthrosis chondrocyte proliferation and apoptosis via Wnt/β-catenin signaling. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 25 29217163
2024 Fusobacterium nucleatum-driven CX3CR1+ PD-L1+ phagocytes route to tumor tissues and reshape tumor microenvironment. Gut microbes 24 39710592
2023 The CX3CL1-CX3CR1 chemokine axis can contribute to tumor immune evasion and blockade with a novel CX3CR1 monoclonal antibody enhances response to anti-PD-1 immunotherapy. Frontiers in immunology 24 37771579
2021 Potential biomarkers reflecting inflammation in patients with severe periodontitis: Fractalkine (CX3CL1) and its receptor (CX3CR1). Journal of periodontal research 24 33641164
2021 CD40 and CD80/86 signaling in cDC1s mediate effective neoantigen vaccination and generation of antigen-specific CX3CR1+ CD8+ T cells. Cancer immunology, immunotherapy : CII 23 34037810
2017 Fractalkine induces angiogenic potential in CX3CR1-expressing monocytes. Journal of leukocyte biology 23 28978662
2013 Early expression of the fractalkine receptor CX3CR1 in pancreatic carcinogenesis. British journal of cancer 23 24084767
2003 Genomic organization and evolution of the CX3CR1/CCR8 chemokine receptor locus. The Journal of biological chemistry 21 12551893

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