Affinage

CX3CR1

CX3C chemokine receptor 1 · UniProt P49238

Length
355 aa
Mass
40.4 kDa
Annotated
2026-04-28
100 papers in source corpus 26 papers cited in narrative 25 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CX3CR1 is a Gi-coupled chemokine receptor for fractalkine (CX3CL1) that transduces survival, migration, and activation signals across diverse cell types including monocytes, microglia, neurons, endothelial cells, and pancreatic β cells. In monocytes and macrophages, CX3CR1 engages AKT/ERK signaling to upregulate Bcl-2 and promote cell survival, thereby controlling non-classical monocyte homeostasis, atherosclerotic foam cell persistence, and hepatic macrophage differentiation (PMID:18971423, PMID:29415879, PMID:21038415). In the central nervous system, CX3CR1 on microglia restrains IL-1β production to maintain hippocampal LTP and cognitive function, while neuronal CX3CR1 activates PI3K/Akt–NF-κB neuroprotective signaling; in the retina it governs microglial repopulation and cone photoreceptor maturation (PMID:22072675, PMID:10869418, PMID:29669747). CX3CR1 also serves non-canonical roles as a receptor for extracellular Tau on microglia (mediating phagocytic clearance inhibited by Tau phosphorylation at S396), as an entry receptor for respiratory syncytial virus on airway epithelial cells, and as a potentiator of glucose-stimulated insulin secretion in pancreatic β cells through intracellular Ca²⁺ mobilization (PMID:28810892, PMID:31726465, PMID:23582329).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2000 High

    Establishing that CX3CR1 is expressed on neurons and directly mediates neuroprotection answered whether fractalkine signaling in the CNS acts only through microglia or also through neuron-autonomous mechanisms.

    Evidence Primary hippocampal neuron cultures with PI3K inhibitors, Akt activators, and anti-CX3CR1 antibody blockade

    PMID:10869418

    Open questions at the time
    • Downstream transcriptional targets of neuronal CX3CR1-NF-κB signaling uncharacterized
    • In vivo relevance of neuron-autonomous CX3CR1 signaling not directly tested
  2. 2003 Medium

    Characterization of the human CX3CR1 promoter architecture — three promoters driving distinct first exons — revealed how tissue- and context-specific transcription of CX3CR1 is organized and showed evolutionary divergence from the mouse gene.

    Evidence Luciferase reporter assays of promoter fragments, genomic sequencing, evolutionary comparison with CCR8

    PMID:12551893

    Open questions at the time
    • Cell-type-specific promoter usage in vivo not mapped
    • Transcription factor occupancy at identified elements not validated by ChIP
  3. 2005 High

    Demonstrating that CX3CR1 is required for transepithelial dendrite formation by lamina propria dendritic cells established its non-redundant role in intestinal immune surveillance and pathogen clearance.

    Evidence CX3CR1-knockout mice with intravital imaging and entero-invasive bacterial challenge

    PMID:15653504

    Open questions at the time
    • Downstream signaling pathway linking CX3CR1 to dendrite extension in DCs not defined
    • Contribution of membrane-bound vs. soluble CX3CL1 not resolved
  4. 2007 High

    Identification of JAK2/STAT5-dependent ICAM-1 upregulation in endothelial cells revealed that CX3CR1 couples to JAK/STAT in addition to canonical Gi pathways, explaining how fractalkine promotes leukocyte adhesion.

    Evidence siRNA knockdown of CX3CR1 and STAT5 in endothelial cells with neutrophil adhesion assay and mouse heart perfusion

    PMID:17885215

    Open questions at the time
    • How CX3CR1-Gi coupling activates JAK2 is mechanistically unresolved
    • Relative contribution of endothelial vs. leukocyte CX3CR1 in vivo not separated
  5. 2008 High

    Genetic rescue with a Bcl-2 transgene proved that CX3CR1's principal role in non-classical monocyte homeostasis is anti-apoptotic survival signaling, linking receptor loss to monocytopenia and reduced atherosclerosis.

    Evidence CX3CR1/CX3CL1 KO mice, Bcl-2 transgene rescue, bone marrow chimeras, human monocyte cell death assay

    PMID:18971423

    Open questions at the time
    • Whether AKT or ERK is the dominant pathway upstream of Bcl-2 in vivo not resolved
    • Kinetics of monocyte death after CX3CL1 withdrawal not defined
  6. 2010 High

    Extending the survival-signaling model to hepatic macrophages showed that CX3CR1 prevents pro-inflammatory macrophage polarization and liver fibrosis, establishing CX3CR1 as a rheostat between macrophage survival and inflammatory differentiation.

    Evidence CX3CR1-KO mice in CCl4 and bile duct ligation fibrosis models with bone marrow chimeras and Bcl-2 expression analysis

    PMID:21038415

    Open questions at the time
    • Whether TNF/iNOS skewing upon CX3CR1 loss is cell-intrinsic or secondary to reduced Bcl-2 not fully distinguished
  7. 2011 High

    Pharmacological rescue of hippocampal LTP and cognitive deficits in CX3CR1-KO mice by IL-1β receptor antagonism placed CX3CR1 as a microglial brake on IL-1β release that is required for normal synaptic plasticity.

    Evidence CX3CR1-KO mice, fear conditioning, Morris water maze, LTP recording, IL-1RA intracerebroventricular infusion

    PMID:22072675

    Open questions at the time
    • Molecular mechanism by which CX3CR1 suppresses IL-1β transcription or processing in microglia not identified
    • Contribution of neuronal vs. microglial CX3CR1 not separated in this model
  8. 2013 High

    Discovery that CX3CR1 on pancreatic β cells mobilizes intracellular Ca²⁺ to potentiate insulin secretion expanded CX3CR1 biology beyond immune cells to metabolic regulation.

    Evidence CX3CR1-KO mice, isolated islet Ca²⁺ imaging, glucose tolerance tests, gene expression profiling in mouse and human islets

    PMID:23582329

    Open questions at the time
    • G-protein coupling mediating Ca²⁺ release in β cells not defined (Gi typically inhibits Ca²⁺)
    • Relative contribution of β-cell CX3CR1 vs. islet macrophage CX3CR1 not fully separated
  9. 2014 High

    Identification of CX3CR1-dependent monocyte infiltration and ROS-TRPA1 activation in chemotherapy-induced neuropathic pain revealed how peripheral CX3CL1–CX3CR1 signaling translates immune recruitment into sensory neuron sensitization.

    Evidence CX3CR1-KO mice, monocyte adoptive transfer, ROS measurement, TRPA1 antagonist, vincristine allodynia model

    PMID:24743146

    Open questions at the time
    • Source of CX3CL1 in the injured nerve not identified
    • Whether CX3CR1 signaling in monocytes directly controls ROS production or acts indirectly not resolved
  10. 2017 High

    Direct binding of extracellular Tau to CX3CR1, with competition against CX3CL1, identified CX3CR1 as a microglial receptor for Tau clearance and showed that S396 phosphorylation impairs this interaction — providing a mechanism linking Tau pathology to deficient phagocytic clearance.

    Evidence Affinity chromatography, Tau-CX3CL1 competition, Cy5-Tau uptake in primary microglia and CX3CR1-KO mouse brain

    PMID:28810892

    Open questions at the time
    • Structural basis of Tau-CX3CR1 interaction unknown
    • Whether Tau binding activates or inhibits CX3CR1 signaling not determined
  11. 2017 High

    Sex-dimorphic regulation of hypothalamic CX3CL1–CX3CR1 explained why female mice resist diet-induced obesity: CX3CR1 restrains hypothalamic microglial activation and metabolic inflammation in a sex-dependent manner.

    Evidence CX3CR1-KO mice, central CX3CL1 pharmacological and viral overexpression, microglial activation assays, metabolic phenotyping

    PMID:28223698

    Open questions at the time
    • Hormonal regulation of CX3CL1/CX3CR1 expression not mechanistically defined
    • Downstream microglial effectors linking CX3CR1 to weight regulation not identified
  12. 2018 Medium

    Demonstrating that CX3CR1 loss disrupts cilium protein localization and cone photoreceptor maturation revealed a non-canonical developmental role for microglial CX3CR1 signaling in retinal cell differentiation.

    Evidence CX3CR1-KO mice, ERG, immunofluorescence for Rpgr/Rpgrip1/centrin, gene expression profiling

    PMID:29669747

    Open questions at the time
    • Whether microglia directly regulate cilium gene expression or act via a secreted factor is unknown
    • Single-study finding; independent replication needed
  13. 2018 Medium

    The homozygous CX3CR1-M280 human variant abolished AKT and ERK phosphorylation without affecting surface expression, confirming that the survival-signaling defect is due to impaired coupling rather than trafficking and validating the mouse KO findings in human primary cells.

    Evidence Primary monocytes from WT, heterozygous, and homozygous M280 donors with phospho-AKT/ERK assays and cell death measurement

    PMID:29415879

    Open questions at the time
    • Structural basis of M280-induced signaling defect unknown
    • Clinical consequences of homozygous M280 on monocyte counts in larger cohorts not established
  14. 2021 Medium

    Identification of CX3CR1 as an entry receptor for RSV on airway epithelial cells extended CX3CR1 function beyond chemokine signaling to viral pathogenesis, demonstrating that blocking the CX3CR1–RSV interaction reduces viral load.

    Evidence Primary differentiated pediatric airway epithelial cells, CX3CR1-blocking antibody, in vivo cotton rat model

    PMID:31726465 PMID:34037420

    Open questions at the time
    • Molecular details of RSV G protein–CX3CR1 binding interface not structurally defined
    • Whether CX3CR1 mediates viral entry or post-binding steps not separated
  15. 2022 High

    High-resolution cryo-EM structures of apo and CX3CL1-bound CX3CR1–Gi1 complexes revealed an atypically small helix VI movement upon activation and identified three structural cholesterol molecules essential for signaling, providing the first atomic-level framework for CX3CR1 pharmacology.

    Evidence Cryo-EM at 2.8 Å and 3.4 Å resolution with mutagenesis and functional signaling assays

    PMID:35767622

    Open questions at the time
    • How cholesterol dependence relates to lipid raft requirement in cell-type-specific signaling not tested
    • Structural basis for Tau binding at CX3CR1 not addressed

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: (1) how CX3CR1-Gi coupling activates JAK/STAT and Ca²⁺ mobilization pathways that are atypical for Gi-linked receptors; (2) whether Tau and CX3CL1 compete at overlapping or distinct CX3CR1 binding sites; and (3) how tissue-specific CX3CR1 promoter usage controls its diverse cell-type expression pattern in vivo.
  • No reconstituted system testing CX3CR1 coupling to JAK/STAT independent of Gi
  • No co-crystal or cryo-EM structure of Tau–CX3CR1
  • No in vivo promoter-usage map across cell types

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 5 GO:0098772 molecular function regulator activity 3
Localization
GO:0005886 plasma membrane 6
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-168256 Immune System 5 R-HSA-112316 Neuronal System 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-1643685 Disease 2
Partners
AKT1BCL2CX3CL1GNAI1JAK2MAPTSTAT5A
Complex memberships
CX3CR1-Gi1 complex

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2022 Cryo-EM structures of CX3CR1-Gi1 complexes in ligand-free and CX3CL1-bound states revealed the structural basis for CX3CL1 recognition, identified key residues governing ligand binding shared with US28, and showed that three cholesterol molecules stabilize conformation and are essential for signaling transduction — with notably smaller helix VI conformational change upon activation compared to other class A GPCR-Gi complexes. Cryo-electron microscopy at 2.8 Å and 3.4 Å resolution, combined with functional binding/signaling assays and mutagenesis Science advances High 35767622
2005 CX3CR1 is required for lamina propria dendritic cells to form transepithelial dendrites that sample luminal antigens, and controls clearance of entero-invasive pathogens; CX3CR1-deficient mice fail to form these dendrites. CX3CR1-knockout mice, intravital imaging, bacterial challenge models Science (New York, N.Y.) High 15653504
2008 CX3CR1 provides an essential survival signal to Gr1low/non-classical monocytes; absence of CX3CR1 or CX3CL1 reduces Gr1low blood monocyte levels, and this is rescued by a Bcl2 transgene. CX3CL1 directly rescues cultured human monocytes from induced cell death, and enforced monocyte/foam cell survival restores atherogenesis in CX3CR1-deficient mice. CX3CR1/CX3CL1 knockout mice, Bcl2 transgene rescue, in vitro cell death assay with human monocytes, bone marrow transplantation chimeras, atherosclerosis model Blood High 18971423
2000 CX3CR1 is expressed on hippocampal neurons (not only microglia); fractalkine activation of neuronal CX3CR1 induces PI3K/Akt activation and NF-κB nuclear translocation, and protects neurons from gp120-induced neurotoxicity in a PI3K/Akt-dependent manner. Immunofluorescence, receptor binding, PI3K inhibitors, Akt activator, anti-CX3CR1 antibody blockade in primary hippocampal neuron cultures Proceedings of the National Academy of Sciences of the United States of America High 10869418
2011 CX3CR1 deficiency in mice impairs hippocampal long-term potentiation (LTP) and causes contextual fear conditioning and Morris water maze deficits; the cognitive and LTP deficits are reversed by IL-1β receptor antagonist infusion, placing CX3CR1 upstream of IL-1β-mediated suppression of synaptic plasticity. CX3CR1-/- mice, fear conditioning, Morris water maze, LTP electrophysiology, IL-1β receptor antagonist rescue The Journal of neuroscience High 22072675
2010 CX3CR1 limits liver fibrosis by controlling differentiation and survival of intrahepatic monocyte-derived macrophages; CX3CR1 activates anti-apoptotic Bcl2 expression in hepatic monocytes, and its absence causes monocytes to preferentially differentiate into pro-inflammatory TNF/iNOS-producing macrophages, increasing fibrosis. CX3CR1-/- mice, two liver fibrosis models (CCl4, bile duct ligation), bone marrow transplantation chimeras, Bcl2 expression analysis Hepatology (Baltimore, Md.) High 21038415
2013 CX3CR1 is expressed on pancreatic islet β cells; its activation by fractalkine increases intracellular Ca2+ and potentiates glucose- and GLP1-stimulated insulin secretion. CX3CR1 KO mice have defective insulin secretion, and FKN treatment upregulates genes required for the differentiated β cell state. CX3CR1 KO mice, isolated islet functional assays, in vivo glucose tolerance tests, intracellular Ca2+ imaging, gene expression analysis Cell High 23582329
2017 Tau protein directly binds CX3CR1 (demonstrated by affinity chromatography and competition with CX3CL1), triggering its internalization by microglia; S396 phosphorylation of Tau decreases its binding affinity to CX3CR1, impairing microglial phagocytosis. Affinity chromatography, Tau-CX3CL1 competition assay, Cy5-Tau uptake in primary microglia cultures and stereotaxic injection into CX3CR1-/- mice Molecular neurodegeneration High 28810892
2007 Fractalkine (CX3CL1) upregulates ICAM-1 expression in endothelial cells through CX3CR1 (expressed on endothelial cells) via activation of the Jak2/Stat5 signaling pathway, promoting neutrophil adhesion. RT-PCR, Western blot, siRNA knockdown of CX3CR1 and Stat5, confocal microscopy, neutrophil adhesion assay, mouse heart perfusion model Circulation research High 17885215
2014 CX3CR1+ monocytes infiltrate the sciatic nerve in response to vincristine treatment via CX3CL1 signaling; these monocytes produce reactive oxygen species that activate TRPA1 in sensory neurons to evoke neuropathic pain. CX3CR1-deficient mice show delayed allodynia. CX3CR1-/- mice, monocyte transfer, ROS measurement, TRPA1 pharmacology, allodynia assay The Journal of clinical investigation High 24743146
2017 Female mice maintain hypothalamic CX3CL1-CX3CR1 signaling on high-fat diet while males show reduced expression; female CX3CR1 knockout mice develop male-like hypothalamic microglial accumulation and diet-induced obesity, and increasing brain CX3CL1 in males reduces microglial activation and weight gain. CX3CR1 KO mice, central pharmacological CX3CL1 administration, virally mediated hypothalamic CX3CL1 overexpression, microglial activation assays, metabolic phenotyping Nature communications High 28223698
2017 CX3CR1high Ly6Clow peripheral monocytes impair motor learning and learning-related dendritic spine plasticity through TNF-α-dependent mechanisms following peripheral immune activation, without requiring microglial function in the CNS. Two-photon in vivo imaging of dendritic spines, monocyte depletion, CX3CR1-GFP mice, TNF-α blockade, learning behavioral assays Nature medicine High 28504723
2002 TGF-β1 upregulates CX3CR1 mRNA and protein (125I-fractalkine binding sites) in rat microglia, and blunts fractalkine-stimulated ERK1/2 phosphorylation. The half-life of CX3CR1 mRNA is unaltered, and two Smad binding elements were identified in the rat CX3CR1 promoter, suggesting transcriptional regulation. Primary rat microglia cultures, radiolabeled fractalkine binding assay, ERK1/2 phosphorylation assay, mRNA stability assay, promoter analysis Journal of neuroimmunology Medium 12446007
2018 Microglial repopulation in the adult retina following ablation is regulated by CX3CL1-CX3CR1 signaling; CX3CR1 deficiency slows repopulation while exogenous CX3CL1 accelerates it. Repopulating microglia under normal CX3CR1 signaling fully restore microglial functions including synaptic maintenance. In vivo imaging, cell-fate mapping, CX3CR1 KO mice, exogenous CX3CL1 administration, retinal electrophysiology Science advances Medium 29750189
2018 Loss of Cx3cr1 in microglia leads to altered cilium protein distribution (Rpgr, Rpgrip1, centrin), failure of cone photoreceptor outer segment elongation, and subsequent cone photoreceptor death during postnatal retinal maturation. Cx3cr1-/- mice, ERG functional testing, immunofluorescence, bead-chip gene array, quantitative PCR, cilium protein localization The Journal of neuroscience Medium 29669747
2018 CX3CR1 activation by fractalkine promotes hematoma resolution and neurological recovery after germinal matrix hemorrhage via the AMPK/PPARγ signaling pathway, promoting M2 microglial polarization; CRISPR knockout or pharmacological inhibition of CX3CR1 abolished these effects. Rat GMH model, recombinant fractalkine intranasal administration, CX3CR1 CRISPR KO, selective CX3CR1 inhibitor (AZD8797), liposome-encapsulated AMPK/PPARγ inhibitors, Western blot, ELISA, immunofluorescence Stroke Medium 37465997
2018 The homozygous CX3CR1-M280 variant impairs CX3CL1-mediated monocyte survival by abolishing AKT and ERK activation downstream of CX3CR1, without affecting receptor surface expression; heterozygous M280 carriers retain survival signaling. Primary monocytes from WT, heterozygous, and homozygous M280 donors; cell death assays; AKT and ERK phosphorylation; blood monocyte counts JCI insight Medium 29415879
2019 CX3CL1-CX3CR1 interaction between mesothelial cells and macrophages promotes TGFβ-driven peritoneal fibrosis; TGFβ upregulates CX3CR1 on monocytic cells (forming a positive feedback loop), and CX3CR1-expressing macrophages promote mesothelial CX3CL1 and TGFβ expression via direct contact. CX3CR1 KO mice, peritoneal dialysis model, in vitro macrophage-mesothelial co-culture, TGFβ stimulation assays Kidney international Medium 30948201
2012 Fractalkine signals through CX3CR1 to activate JAK/STAT pathway in cerulein-stimulated pancreatic AR42J cells; blocking FKN with siRNA or inhibiting JAK with AG490 reduces TNF-α expression in a severe acute pancreatitis rat model. siRNA knockdown, AG490 JAK inhibitor, Western blot, RT-PCR, immunofluorescence, in vivo SAP rat model Inflammation Medium 22213034
2019 CX3CR1 inhibition blocks migration of tendon-resident CX3CR1+/CX3CL1+ 'tenophages' in 3D tendon constructs in vitro, indicating that CX3CR1 mediates these cells' migratory behavior. 3D tendon-like construct model, CX3CR1 inhibition, Cx3cr1-reporter transgenic mice, immunofluorescence Disease models & mechanisms Low 31744815
2003 The human CX3CR1 gene is organized with three promoters transcribing three separate exons spliced to a fourth exon containing the coding region; several positive and negative regulatory elements were identified by luciferase reporter assays. Mouse CX3CR1 has a different promoter organization. CX3CR1 and CCR8 arose from duplication of an ancestral gene. Genomic sequencing, luciferase reporter assays, SNP analysis, evolutionary comparison The Journal of biological chemistry Medium 12551893
2021 CX3CR1 functions as a receptor for respiratory syncytial virus (RSV) on pediatric airway epithelial cells; CX3CR1 is expressed on primary differentiated pediatric lung epithelial cells, RSV preferentially infects CX3CR1-positive cells, and blocking CX3CR1/RSV interaction significantly decreases viral load. In situ hybridization, immunohistochemistry, primary pediatric airway epithelial cell cultures, CX3CR1-blocking antibody, viral load assay Pediatric research Medium 31726465 34037420
2020 IL-15 promotes the phenotype, survival (via STAT5 and Bcl-2), and proliferation (via STAT5 and mTORC1) of CX3CR1+CD57+CD8+ T cells in vitro, whereas TCR stimulation leads to their death, identifying the cytokine signaling pathway maintaining this subset. In vitro IL-15 stimulation, STAT5 and Bcl-2 inhibitors, mTORC1 inhibitor, flow cytometry, proliferation and survival assays JCI insight Medium 32369455
2017 CX3CR1 regulates osteoarthritic chondrocyte proliferation and apoptosis through the Wnt/β-catenin signaling pathway; siCX3CR1 transfection increased nuclear β-catenin, Cyclin D1, and MMP-13, and these effects were abolished by the Wnt inhibitor XAV-939. siRNA knockdown in OA chondrocytes, Wnt inhibitor XAV-939, Western blot, qRT-PCR, MTT assay, flow cytometry Biomedicine & pharmacotherapy Low 29217163
2022 In arthritis, CX3CR1 deletion reduces acute nociception and DRG non-classical monocyte numbers; in vitro, CGRP liberates CX3CL1 from endothelium and FKN via CX3CR1 activates intracellular kinases in bone marrow-derived macrophages, polarizing them toward M1-like phenotype and promoting IL-6 release. CX3CR1 KO mice, K/BxN serum transfer arthritis model, DRG macrophage phenotyping, in vitro CGRP/FKN signaling assay in BMDM, kinase activation assays Brain, behavior, and immunity Medium 36115544

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 CX3CR1-mediated dendritic cell access to the intestinal lumen and bacterial clearance. Science (New York, N.Y.) 1243 15653504
2011 CX3CR1 deficiency leads to impairment of hippocampal cognitive function and synaptic plasticity. The Journal of neuroscience : the official journal of the Society for Neuroscience 514 22072675
2008 CX3CR1 is required for monocyte homeostasis and atherogenesis by promoting cell survival. Blood 393 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 275 24352739
2015 Functional classification of memory CD8(+) T cells by CX3CR1 expression. Nature communications 234 26404698
2014 The atypical chemokine receptor CCRL1 shapes functional CCL21 gradients in lymph nodes. Nature immunology 231 24813163
2010 The fractalkine receptor CX₃CR1 protects against liver fibrosis by controlling differentiation and survival of infiltrating hepatic monocytes. Hepatology (Baltimore, Md.) 218 21038415
2018 Microglia and Aging: The Role of the TREM2-DAP12 and CX3CL1-CX3CR1 Axes. International journal of molecular sciences 216 29361745
2020 The Impact of the CX3CL1/CX3CR1 Axis in Neurological Disorders. Cells 202 33065974
2014 Modulating neurotoxicity through CX3CL1/CX3CR1 signaling. Frontiers in cellular neuroscience 186 25152714
2017 Absence of CX3CR1 impairs the internalization of Tau by microglia. Molecular neurodegeneration 178 28810892
2018 LAG3+ Regulatory T Cells Restrain Interleukin-23-Producing CX3CR1+ Gut-Resident Macrophages during Group 3 Innate Lymphoid Cell-Driven Colitis. Immunity 168 30097293
2015 Loss of CX3CR1 increases accumulation of inflammatory monocytes and promotes gliomagenesis. Oncotarget 159 25987130
2010 Tickets to the brain: role of CCR2 and CX3CR1 in myeloid cell entry in the CNS. Journal of neuroimmunology 147 20554025
2014 Monocytes expressing CX3CR1 orchestrate the development of vincristine-induced pain. The Journal of clinical investigation 144 24743146
2017 Sex differences in microglial CX3CR1 signalling determine obesity susceptibility in mice. Nature communications 142 28223698
2021 CX3CL1/CX3CR1 signaling targets for the treatment of neurodegenerative diseases. Pharmacology & therapeutics 141 34492237
2007 CX3CR1 deficiency impairs dendritic cell accumulation in arterial intima and reduces atherosclerotic burden. Arteriosclerosis, thrombosis, and vascular biology 139 18079406
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
2017 CX3CR1+ monocytes modulate learning and learning-dependent dendritic spine remodeling via TNF-α. Nature medicine 111 28504723
2013 Chemokines and atherosclerosis: focus on the CX3CL1/CX3CR1 pathway. Acta pharmacologica Sinica 109 23974513
2018 Repopulating retinal microglia restore endogenous organization and function under CX3CL1-CX3CR1 regulation. Science advances 107 29750189
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 97 28125278
2010 Fractalkine/CX3CR1: why a single chemokine-receptor duo bears a major and unique therapeutic potential. Expert opinion on therapeutic targets 93 20055718
2019 Cx3CR1 Expression Identifies Distinct Macrophage Populations That Contribute Differentially to Inflammation and Repair. ImmunoHorizons 91 31356156
2017 The role of microglia and their CX3CR1 signaling in adult neurogenesis in the olfactory bulb. eLife 90 29251592
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
2019 Targeting Microglia Using Cx3cr1-Cre Lines: Revisiting the Specificity. eNeuro 84 31201215
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 80 32755573
2010 Role of CX3CR1/CX3CL1 axis in primary and secondary involvement of the nervous system by cancer. Journal of neuroimmunology 79 20630606
2019 CX3CL1-CX3CR1 interaction mediates macrophage-mesothelial cross talk and promotes peritoneal fibrosis. Kidney international 75 30948201
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
2011 Fractalkine/CX3CR1 signalling in chronic pain and inflammation. Current pharmaceutical biotechnology 66 21466443
2010 CX3CR1/CX3CL1 axis negatively controls glioma cell invasion and is modulated by transforming growth factor-β1. Neuro-oncology 65 20511186
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
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 63 19001328
2021 Fractalkine (CX3CL1) and Its Receptor CX3CR1: A Promising Therapeutic Target in Chronic Kidney Disease? Frontiers in immunology 62 34163473
2014 CX3CR1 is a modifying gene of survival and progression in amyotrophic lateral sclerosis. PloS one 60 24806473
2007 Fractalkine upregulates intercellular adhesion molecule-1 in endothelial cells through CX3CR1 and the Jak Stat5 pathway. Circulation research 56 17885215
2012 Therapeutic potential of the chemokine-receptor duo fractalkine/CX3CR1: an update. Expert opinion on therapeutic targets 55 22530606
2020 Inflammescent CX3CR1+CD57+CD8+ T cells are generated and expanded by IL-15. JCI insight 51 32369455
2020 Dissecting the phenotypic and functional heterogeneity of mouse inflammatory osteoclasts by the expression of Cx3cr1. eLife 51 32400390
2016 Up-regulated fractalkine (FKN) and its receptor CX3CR1 are involved in fructose-induced neuroinflammation: Suppression by curcumin. Brain, behavior, and immunity 51 26765996
2015 CX3CR1 is dysregulated in blood and brain from schizophrenia patients. Schizophrenia research 51 26285829
2019 Crosstalk between the CX3CL1/CX3CR1 Axis and Inflammatory Signaling Pathways in Tissue Injury. Current protein & peptide science 50 30843484
2014 Differential expression of the fractalkine chemokine receptor (CX3CR1) in human monocytes during differentiation. Cellular & molecular immunology 50 25502213
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
2019 CX3CR1 as a respiratory syncytial virus receptor in pediatric human lung. Pediatric research 46 31726465
2016 Therapeutic intervention of inflammatory/immune diseases by inhibition of the fractalkine (CX3CL1)-CX3CR1 pathway. Inflammation and regeneration 46 29259682
2022 Activation of the human chemokine receptor CX3CR1 regulated by cholesterol. Science advances 45 35767622
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
2002 Fractalkine expression and the recruitment of CX3CR1+ cells in the prolonged mesangial proliferative glomerulonephritis. Kidney international 44 12028445
2017 CX3CL1/CX3CR1 Axis, as the Therapeutic Potential in Renal Diseases: Friend or Foe? Current gene therapy 43 29446734
2021 Regulation and function of CX3CR1 and its ligand CX3CL1 in kidney disease. Cell and tissue research 41 34009468
2020 Revising CX3CR1 Expression on Murine Classical and Non-classical Monocytes. Frontiers in immunology 41 32582197
2019 Tenophages: a novel macrophage-like tendon cell population expressing CX3CL1 and CX3CR1. Disease models & mechanisms 41 31744815
2013 Fractalkine (CX3CL1) and its receptor CX3CR1 may contribute to increased angiogenesis in diabetic placenta. Mediators of inflammation 41 23956503
2012 Ccl2, Cx3cr1 and Ccl2/Cx3cr1 chemokine deficiencies are not sufficient to cause age-related retinal degeneration. Experimental eye research 41 23232206
2004 Fractalkine and its receptor, CX3CR1, upregulation in streptozotocin-induced diabetic kidneys. Nephron. Experimental nephrology 40 15153757
2024 CX3CL1 (Fractalkine)-CX3CR1 Axis in Inflammation-Induced Angiogenesis and Tumorigenesis. International journal of molecular sciences 39 38731899
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 38 28450294
2020 Role of CX3CR1 signaling in malignant transformation of gliomas. Neuro-oncology 37 32236410
2022 Dorsal root ganglia CX3CR1 expressing monocytes/macrophages contribute to arthritis pain. Brain, behavior, and immunity 33 36115544
2006 Association study between the CX3CR1 gene and asthma. Genes and immunity 33 17082760
2023 Fractalkine/CX3CR1-Dependent Modulation of Synaptic and Network Plasticity in Health and Disease. Neural plasticity 32 36644710
2018 MicroRNA-195 protection against focal cerebral ischemia by targeting CX3CR1. Journal of neurosurgery 32 30497184
2014 CX3CL1/CX3CR1 and CCL2/CCR2 chemokine/chemokine receptor complex in patients with AMD. PloS one 31 25503251
2023 Fractalkine Enhances Hematoma Resolution and Improves Neurological Function via CX3CR1/AMPK/PPARγ Pathway After GMH. Stroke 30 37465997
2021 Dynamic role of macrophage CX3CR1 expression in inflammatory bowel disease. Immunology letters 30 33582183
2014 Intermediate expression of CCRL1 reveals novel subpopulations of medullary thymic epithelial cells that emerge in the postnatal thymus. European journal of immunology 30 25070355
2014 Overexpression of CX3CR1 is associated with cellular metastasis, proliferation and survival in gastric cancer. Oncology reports 30 25482732
2015 Metabolic Effects of CX3CR1 Deficiency in Diet-Induced Obese Mice. PloS one 29 26393344
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 T Cell CX3CR1 Mediates Excess Atherosclerotic Inflammation in Renal Impairment. Journal of the American Society of Nephrology : JASN 28 26449606
2015 Expression pattern of Ccr2 and Cx3cr1 in inherited retinal degeneration. Journal of neuroinflammation 28 26458944
2012 Fractalkine upregulates inflammation through CX3CR1 and the Jak-Stat pathway in severe acute pancreatitis rat model. Inflammation 28 22213034
2011 Chemokine receptor CX3CR1 promotes dendritic cell development under steady-state conditions. European journal of immunology 28 21425158
2013 Interaction between CX3CL1 and CX3CR1 regulates vasculitis induced by immune complex deposition. The American journal of pathology 27 23470165
2010 Impact of chemokine receptor CX3CR1 in human renal allograft rejection. Transplant immunology 27 20600902
2019 Role of CX3CL1/CX3CR1 Signaling Axis Activity in Osteoporosis. Mediators of inflammation 26 31780870
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
2021 Potential biomarkers reflecting inflammation in patients with severe periodontitis: Fractalkine (CX3CL1) and its receptor (CX3CR1). Journal of periodontal research 24 33641164
2021 CX3CR1 Is a Receptor for Human Respiratory Syncytial Virus in Cotton Rats. Journal of virology 24 34037420
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 23 37771579
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 22 24084767
2003 Genomic organization and evolution of the CX3CR1/CCR8 chemokine receptor locus. The Journal of biological chemistry 21 12551893