Affinage

CX3CL1

Fractalkine · UniProt P78423

Length
397 aa
Mass
42.2 kDa
Annotated
2026-06-09
100 papers in source corpus 30 papers cited in narrative 30 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CX3CL1 (fractalkine) is a membrane-anchored transmembrane chemokine that functions both as a cell-surface adhesion molecule and, after proteolytic release, as a soluble chemoattractant, thereby coupling vascular leukocyte recruitment to chemokine signaling across immune, neural, and tumor contexts (PMID:17467666, PMID:14698146). Its activity is governed by regulated intramembrane proteolysis: ADAM10/ADAM17 alpha-secretase activity sheds the soluble chemokine domain, and gamma-secretase (presenilin-dependent, beta-secretase-independent) then cleaves the remaining C-terminal fragment to liberate an intracellular domain that translocates to the nucleus and reprograms gene expression (PMID:17467666, PMID:31209068). Self-association of its transmembrane domain drives homo-oligomerization (3–7 monomers), which is required for cell-to-cell adhesion, while apical membrane targeting in polarized epithelium depends on N-glycosylation and supports luminal leukocyte capture (PMID:32494000, PMID:17151328). The soluble and membrane-bound forms are functionally distinct in vivo: soluble CX3CL1 more fully restores hippocampal neurogenesis, LTP, and memory in knockout mice, and its nuclear C-terminal fragment promotes adult neurogenesis through a CX3CR1-independent TGFβ2/3–Smad2 axis (PMID:31209068, PMID:31822518, PMID:32410624). Through its receptor CX3CR1, CX3CL1 activates Src/FAK, PI3K/AKT, and RhoA/ROCK signaling to drive cancer cell migration, invasion, and metastasis, and it directs leukocyte and platelet trafficking, M1/M2 macrophage polarization, osteoclastogenesis, and microglial phenotype (PMID:30066854, PMID:32319605, PMID:32799418, PMID:37626378). Its endothelial and stromal expression is transcriptionally induced through NF-κB by pro-inflammatory and vasoactive stimuli including TNF-α, IL-1β, thrombin (via PAR1), and angiotensin II (via Nox5/ERK/p38), positioning CX3CL1 as a convergent effector of inflammatory and metastatic signaling (PMID:18436581, PMID:23117657, PMID:14605272).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 2003 Medium

    Established that CX3CL1 governs NK cell function through adhesion and trafficking rather than direct cytotoxicity, defining its core role as a vascular capture molecule.

    Evidence In vivo radiolabeled tumor clearance with anti-CX3CL1/CX3CR1 blockade plus endothelial adhesion and NK cytolysis assays in mice

    PMID:14698146

    Open questions at the time
    • Did not resolve the soluble vs. membrane-bound contribution to NK adhesion
    • No molecular signaling pathway dissected
  2. 2006 High

    Showed how CX3CL1 is spatially positioned for leukocyte capture by defining the determinants of its polarized apical targeting in epithelium.

    Evidence GFP-tagged CX3CL1 in polarized MDCK cells with FRAP, glycosylation inhibition, fractionation, and leukocyte adhesion assays

    PMID:17151328

    Open questions at the time
    • The trafficking machinery reading the N-glycan signal was not identified
    • Generalizability beyond renal epithelium untested
  3. 2007 High

    Defined the proteolytic logic of CX3CL1 by demonstrating sequential ADAM10/gamma-secretase processing analogous to Notch, establishing regulated intramembrane proteolysis as the switch between membrane and soluble forms.

    Evidence Presenilin 1/2 knockout cells, secretase inhibitors, and tagged CTF-detection constructs with Western blotting

    PMID:17467666

    Open questions at the time
    • Fate and function of the released intracellular fragment not addressed here
    • Physiological triggers of cleavage in vivo not defined
  4. 2008 High

    Connected inflammatory protease signaling to CX3CL1 induction by showing thrombin/PAR1/NF-κB drives endothelial CX3CL1 and downstream monocyte adhesion.

    Evidence HUVEC stimulation with PAR1 agonist/antagonist, NF-κB inhibitors, dominant-negative IκBα, EMSA, and co-culture adhesion/migration assays

    PMID:18436581

    Open questions at the time
    • In vivo relevance to thrombotic inflammation not tested
    • Did not separate soluble from membrane CX3CL1 contributions
  5. 2012 High

    Generalized NF-κB-dependent CX3CL1 induction to vasoactive signaling, with angiotensin II acting via TNF-α and Nox5/ERK/p38 in arterial but not venous endothelium.

    Evidence siRNA knockdown, pathway inhibitors, arterial vs. venous endothelial cells, and CX3CR1-deficient mice with adhesion readouts

    PMID:23117657

    Open questions at the time
    • Basis of arterial-venous selectivity not molecularly defined
    • Link to atherosclerotic disease progression not directly tested
  6. 2019 Medium

    Revealed CX3CL1 back-signaling, showing the nuclear-translocating intracellular domain reduces Alzheimer pathology by enhancing neurogenesis through a receptor-independent TGFβ2/3–Smad2 axis.

    Evidence Transgenic CX3CL1-CTF overexpression in 5xFAD mice with RNA-seq, plus Tg-CX3CL1 mice crossed to Smad2 conditional knockouts and tau models

    PMID:31209068 PMID:31822518

    Open questions at the time
    • Direct DNA-binding or transcriptional targets of the ICD not identified
    • How nuclear ICD activates TGFβ2/3 transcription is unresolved
  7. 2020 High

    Demonstrated that transmembrane-driven homo-oligomerization is mechanistically required for CX3CL1 adhesion, and that soluble and membrane forms are functionally non-equivalent in vivo.

    Evidence Biophysical TM-peptide self-association (native gels, single-molecule kinetics, FRAP) and adhesion inhibition; AAV isoform-specific rescue in CX3CL1-knockout mice with LTP/behavioral readouts

    PMID:32410624 PMID:32494000

    Open questions at the time
    • Structural model of the oligomer interface not resolved
    • Mechanism behind superior soluble-form rescue of memory not defined
  8. 2020 Medium

    Established CX3CL1/CX3CR1 as a pro-metastatic axis, linking shedding (ADAM17/ADAM10) to Src/FAK, PI3K/AKT, and RhoA/ROCK activation that drives tumor cell migration and invasion.

    Evidence Western blot pathway profiling, kinase inhibitors, neutralizing antibodies, knockdown, and in vivo metastasis models across prostate, lung, and hepatocellular cancer

    PMID:30066854 PMID:30628679 PMID:32319605 PMID:38280480

    Open questions at the time
    • Whether autocrine vs. stromal-derived CX3CL1 dominates differs by tumor
    • EGFR Tyr992 transactivation mechanism not generalized across cancers
  9. 2024 Medium

    Positioned CX3CL1 within antitumor immunity, acting as an immunogenic apoptosis 'find me' signal and as an m6A/YTHDF2-stabilized transcript that recruits CD8+ T cells.

    Evidence Recombinant CX3CL1 prophylactic vaccination across cell-death modalities; liver-specific Ythdf2 knockout mice with cGAS-STING and CD8+ recruitment analysis

    PMID:39011040 PMID:39237909

    Open questions at the time
    • Receptor/cell type sensing the 'find me' signal not pinned down
    • Direct demonstration that m6A-stabilized CX3CL1 transcript yields functional protein gradient incomplete

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CX3CL1 cleavage state, oligomerization, and the soluble/membrane/intracellular-domain triad are coordinately regulated to dictate context-specific outcomes remains unresolved.
  • No unified structural model linking TM oligomerization to receptor engagement
  • Transcriptional program of the nuclear ICD not mapped genome-wide
  • Determinants selecting adhesion vs. chemoattraction vs. back-signaling in a given tissue undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 3 GO:0060089 molecular transducer activity 2 GO:0098631 cell adhesion mediator activity 2 GO:0005198 structural molecule activity 1
Localization
GO:0005886 plasma membrane 3 GO:0005576 extracellular region 2 GO:0005634 nucleus 1
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 4 R-HSA-168256 Immune System 4 R-HSA-392499 Metabolism of proteins 2
Partners
ADAM10ADAM17CX3CR1

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 CX3CL1 is sequentially processed by alpha-secretase (ADAM10) and then gamma-secretase, generating C-terminal fragments (CTFs). ADAM10-mediated ectodomain shedding at multiple cleavage sites releases the soluble chemokine domain, and inhibitor studies plus presenilin 1/2-deficient cell lines established gamma-secretase (but not beta-secretase) involvement in processing the remaining CTF, analogous to Notch/E-cadherin processing. Inhibitor studies, presenilin 1/2 knockout cell lines, CX3CL1 constructs C-terminally fused to 2Z-tag for CTF detection, Western blotting Biochemical and biophysical research communications High 17467666
2020 CX3CL1 forms homo-oligomers of 3–7 monomers driven by its transmembrane domain. The transmembrane peptide self-associates in both cellular and acellular lipid environments (while a scrambled version does not), and a transmembrane peptide inhibitor blocks both CX3CL1 oligomerization and its adhesive function, demonstrating that oligomerization is required for cell-to-cell adhesion. Native electrophoresis, single-molecule fluorescence kinetics, FRAP assays with transmembrane peptides in cells and liposomes, molecular modeling, adhesion inhibition assays Scientific reports High 32494000
2019 The CX3CL1 intracellular domain (CX3CL1-ICD), released by sequential α-, β-, and γ-secretase cleavage, translocates to the cell nucleus and alters gene expression (back-signaling). Overexpression of the CX3CL1 C-terminal fragment in 5xFAD Alzheimer mice reduced amyloid deposition and neuronal loss; this effect was attributed to enhanced neurogenesis through activation of the TGFβ2/3-Smad2/3 pathway and was independent of CX3CR1 binding. Transgenic mouse overexpression, morphological and unbiased RNA-sequencing analyses, immunofluorescence, genetic epistasis in 5xFAD model The Journal of experimental medicine Medium 31209068
2019 CX3CL1 overexpression in neurons (Tg-CX3CL1 mice) enhances adult neurogenesis in subgranular and subventricular zones via upregulation of TGF-β2 and TGF-β3 and activation of downstream Smad2 signaling. Neuronal deletion of Smad2 mitigated CX3CL1-enhanced neurogenesis, placing CX3CL1 upstream of TGF-β2/3-Smad2 in the neurogenesis pathway. Transgenic mouse overexpression, Smad2 conditional knockout, crossing with PS19 tau mice, behavioral testing, genetic epistasis The Journal of neuroscience Medium 31822518
2020 Soluble CX3CL1 (sFKN) and membrane-bound CX3CL1 (mFKN) exhibit differential activities in vivo: AAV-delivered sFKN fully rescued hippocampal neurogenesis, long-term potentiation, and both long-term and spatial memory deficits in CX3CL1-knockout mice, whereas mFKN only partially restored spatial learning and did not rescue long-term memory or neurogenesis. CX3CL1 knockout mice, AAV gene delivery of two CX3CL1 isoforms, behavioral cognitive testing, hippocampal neurogenesis assays, LTP electrophysiology Journal of neuroinflammation Medium 32410624
2006 In polarized renal tubular epithelial cells (MDCK), CX3CL1 is targeted to and immobilized at the apical membrane. Apical targeting depends on N-linked glycosylation but not on the intracellular domain, lipid raft association, O-glycosylation, or direct actin cytoskeleton association (FRAP and fractionation showed membrane immobility but triton-soluble partitioning). Apically localized CX3CL1 enhanced CX3CR1-expressing leukocyte adhesion to the luminal surface. MDCK cell polarization, GFP-tagged CX3CL1, FRAP, cholesterol depletion, N-glycosylation inhibition, triton fractionation, leukocyte adhesion assays Journal of the American Society of Nephrology High 17151328
2008 Thrombin induces endothelial CX3CL1 expression via protease-activated receptor 1 (PAR1) activation and downstream NF-κB signaling. Membrane-anchored CX3CL1 induced on HUVEC by thrombin triggers monocyte adhesion and enhanced CCL2/MCP-1 release by monocytes, potentiating transendothelial migration. The effect was blocked by NF-κB inhibitors and a PAR1 antagonist. RT-PCR, Western blot, flow cytometry, EMSA, ELISA, PAR1 agonist peptide, PAR1 antagonist SCH79797, IκB kinase inhibitor, dominant-negative IκBα overexpression, co-culture adhesion and migration assays Journal of leukocyte biology High 18436581
2012 ERK pathway activation and ADAM17 (and MMPs) are required for ethanol-induced CX3CL1 shedding/release from pancreatic stellate cells. Ethanol and phorbol ester synergistically increase CX3CL1 release via ERK and ADAM17 activation; specific inhibitors of ERK, MMP, and ADAM each suppressed CX3CL1 release. Primary rat pancreatic stellate cell culture, real-time RT-PCR, Western blot, ELISA, ERK/MMP/ADAM pharmacological inhibitors Laboratory investigation Medium 23147224
2008 CX3CL1 treatment of trophoblast cells (AC1M-88) increases adhesion to fibronectin and regulates expression of more than 30 ECM/adhesion genes including α-catenin (CTNNA1), osteopontin (SPP1), integrin α6 (ITGA6), MMP12, integrin β5 (ITGB5), and ECM1, demonstrating that CX3CL1 promotes trophoblast migration by altering adhesion molecule and ECM profiles. Pathway-specific oligoarrays, quantitative real-time RT-PCR, fibronectin adhesion assay, immunohistochemistry of first-trimester implantation sites Biology of reproduction Medium 18367676
2003 CX3CL1 regulates NK cell activity in vivo: blocking anti-CX3CL1 or anti-CX3CR1 antibodies reduced NK-mediated clearance of YAC-1 tumor cells by 4–5 fold in mice. NK cell binding to activated endothelial monolayers was significantly inhibited by anti-CX3CR1 antibody or soluble CX3CL1. No direct effect on in vitro NK cytolytic activity was detected, indicating the effect operates through adhesion/trafficking rather than direct cytotoxicity. In vivo radiolabeled tumor cell clearance model, anti-CX3CL1/CX3CR1 antibody blocking, in vitro NK cytolysis assay, endothelial adhesion assay Cellular immunology Medium 14698146
2014 CX3CR1 expression by both Th2 and Th1 CD4+ T cells is required for atopic dermatitis (AD) pathology. CX3CR1 deficiency or CX3CL1 blockade profoundly reduced AD but not psoriasis. Adoptive transfer experiments established that CX3CR1 controls CD4+ T cell retention in inflamed skin (not antigen presentation or T cell proliferation), identifying a novel function for this chemokine receptor distinct from its role in asthma where it regulates T cell survival. CX3CR1-deficient mice, CX3CL1 blocking antibody, adoptive transfer of CX3CR1-deficient T cells, murine AD and psoriasis models The Journal of experimental medicine High 24821910
2011 Exogenous CX3CL1 (fractalkine) protects striatal neurons from synergistic morphine + HIV-1 Tat-induced dendritic loss and death through CX3CR1 on microglia: antibody blockade of CX3CR1 mimicked the toxicity, and CX3CL1 failed to protect neurons co-cultured with CX3CR1-null glia, demonstrating that neuroprotection requires glial CX3CR1. CX3CL1 also normalized elevated microglial motility caused by Tat/morphine. Wild-type and Cx3cr1 knockout mouse co-cultures, time-lapse digital microscopy, antibody blockade, ELISA, immunofluorescence, Western blot Molecular neurodegeneration Medium 22093090
2018 CX3CL1 activates the Src/FAK signaling pathway in prostate cancer cells through the Tyr992 residue of EGFR phosphorylation, promoting cell proliferation, migration, invasion and inhibiting apoptosis; kinase inhibitors of Src and FAK blocked CX3CL1-induced migration, and CX3CR1 overexpression promoted spinal metastasis in an in vivo mouse model. Western blot for Src/FAK phosphorylation, siRNA knockdown, kinase inhibitors, Transwell migration/invasion assays, in vivo mouse spinal metastasis model International journal of oncology Medium 30066854
2019 CX3CL1 promotes lung cancer cell (H460) migration and invasion via time-dependent activation of the Src/FAK signaling pathway; blocking Src with saracatinib prevented CX3CL1-mediated migration and invasion without affecting proliferation. Western blot for Src/FAK phosphorylation time-course, Transwell migration/invasion assays, saracatinib pharmacological inhibition Oncology reports Medium 30628679
2010 Endogenous CX3CL1 negatively regulates glioma cell invasion by promoting tumor cell aggregation; neutralizing anti-CX3CL1 antibody delayed tumor aggregation and increased invasiveness. TGF-β1 decreases CX3CL1 mRNA and protein expression in glioma cells (confirmed by both recombinant TGF-β1 treatment and TGF-β1 siRNA knockdown), suggesting TGF-β1-mediated reduction of CX3CL1 contributes to glioma invasiveness. Neutralizing anti-CX3CL1 monoclonal antibody, recombinant TGF-β1 treatment, siRNA knockdown of TGF-β1, RT-PCR, Western blot, cell adhesion and invasion assays Neuro-oncology Medium 20511186
2020 ADAM17-activated by MAPK14 (p38) in bone marrow endothelial cells (BMECs) mediates CX3CL1 shedding and release of soluble CX3CL1, which then promotes migration and invasion of hepatocellular carcinoma cells; neutralization of CX3CL1 inhibited BMEC-enhanced tumor cell migration. CX3CL1 activates the Src/PTK2 signaling axis and downstream PIK3CA/AKT and RHOA/ROCK2 pathways in HCC cells. Neutralizing antibody, Western blot for signaling pathway activation, Transwell assays, MAPK14 activation studies, in vivo mouse spinal metastasis model with CX3CR1 overexpression International journal of oncology Medium 32319605
2024 Platelet-derived TLR4/NF-κB signaling increases ADAM10 expression in HCC tumor cells; ADAM10 then catalyzes CX3CL1 shedding, and the released CX3CL1 binds CX3CR1 to induce epithelial-mesenchymal transition and activate RhoA signaling, promoting tumor cell migration, invasion, and endothelial permeability. TLR4 knockdown or ADAM10 inhibition blocked platelet-enhanced tumor metastasis in vivo. TLR4 siRNA knockdown, ADAM10 inhibition, Western blot, Transwell migration/invasion assays, endothelial permeability assay, in vivo mouse lung metastasis model Cancer letters Medium 38280480
2012 Angiotensin II induces functional CX3CL1 expression in arterial (but not venous) endothelial cells through TNF-α and Nox5/ERK1/2/p38 MAPK/NF-κB signaling, leading to mononuclear cell adhesion. Knockdown of TNF-α or Nox5 with siRNA, or pharmacological inhibition of ERK1/2, p38, or NF-κB, abolished Ang-II-induced CX3CL1 upregulation and monocyte arrest. CX3CR1-deficient mice showed 83% reduction in arteriolar leukocyte adhesion. siRNA knockdown, pharmacological inhibitors (ERK1/2, p38, NF-κB), in vivo CX3CR1-deficient mice, human umbilical arterial vs. venous endothelial cells, mononuclear cell adhesion assays Arteriosclerosis, thrombosis, and vascular biology High 23117657
2003 In glomerulonephritis, activated mesangial cells are a major source of upregulated CX3CL1; TNF-α, IL-1β, PDGF-AB, and bFGF all upregulate CX3CL1 mRNA and protein in cultured mesangial cells. This cytokine/growth factor-stimulated expression is abolished by NF-κB inhibitors (curcumin, MG132), establishing NF-κB as the required transcriptional mediator. Northern blot, Western blot, RT-PCR, in situ hybridization combined with immunohistochemistry, NF-κB inhibitors (curcumin, MG132), rat anti-Thy1 glomerulonephritis model Nephrology, dialysis, transplantation Medium 14605272
2019 AAV8-delivered soluble CX3CL1 (sCX3CL1) significantly prolongs cone photoreceptor survival and improves visual function in three RP mouse strains. Pharmacological depletion of ~99% of microglia failed to abrogate the cone-rescue effect, demonstrating that sCX3CL1 acts via a pathway that does not require normal microglial numbers. AAV8 subretinal injection, three RP mouse strains, pharmacological microglia depletion, RNA sequencing of microglia, visual function testing Proceedings of the National Academy of Sciences High 31036641
2019 CX3CL1 directly induces platelet migration in vitro; CX3CR1/Syk/PI3K pathway components are essential for CX3CL1-induced platelet migration. Hypoxia enhances platelet migration by upregulating CX3CL1 expression in HCC cells. CX3CL1 knockdown in HCC cells reduced platelet infiltration both in vitro and in an orthotopic HCC mouse model. Platelet migration assay, CX3CR1/Syk/PI3K inhibitors, CX3CL1 knockdown, hypoxia treatment, orthotopic HCC mouse model Molecular oncology Medium 32799418
2024 YTHDF2 (an m6A reader) in peritumoral hepatocytes stabilizes CX3CL1 transcripts in an m6A-dependent manner, increasing CX3CL1 expression and CD8+ T cell recruitment to suppress liver tumor growth. Oxaliplatin upregulates YTHDF2 expression via the cGAS-STING pathway, linking chemotherapy-induced innate immune signaling to CX3CL1-mediated adaptive immune responses. Liver-specific Ythdf2 knockout mice, tumor-bearing mouse models, m6A-dependent mRNA stability assays, cGAS-STING pathway analysis, CD8+ T cell recruitment quantification Molecular cancer Medium 39237909
2024 Neuronal cathepsin S (CTSS) overexpression activates the CX3CL1-CX3CR1 axis (and JAK2-STAT3 pathway) to drive microglial activation toward M1 pro-inflammatory phenotype, worsening brain inflammation in aging and AD. The selective CTSS inhibitor LY3000328 rescued AD-related pathological features in APP/PS1 mice. CTSS was further shown to alter cathepsin B and L activities in microglia. CTSS overexpression in neurons, FACS, transcriptome (RNA-seq), CTSS inhibitor LY3000328, APP/PS1 mouse model, immunofluorescence Aging cell Medium 39453382
2013 CX3CR1-CX3CL1 interaction in peritoneal fibrosis: CX3CL1 on peritoneal mesothelial cells interacts with CX3CR1-expressing macrophages in a positive feedback loop—macrophage cytokines (IL-1β) promote mesothelial CX3CL1 and TGF-β expression; TGF-β in turn upregulates CX3CR1 in monocytic cells. CX3CR1 deficiency or deletion protected against dialysate-induced peritoneal fibrosis in mouse models. CX3CR1-deficient mice, peritoneal dialysis mouse model, bone marrow transplantation, in vitro cytokine stimulation of mesothelial/monocytic cells, Western blot Kidney international Medium 30948201
2022 CX3CL1 inhibition in cisplatin-induced acute kidney injury reduces podocyte ferroptosis by attenuating intracellular iron overload, lipid peroxidation (MDA, ROS), and mitochondrial dysfunction, while preserving GPX4 and XCT activity. CX3CL1 inhibition also attenuated endoplasmic reticulum stress (GRP78/eIF2α/CHOP pathway) and HIF-1α/HO-1 expression in podocytes in vitro and in vivo. CX3CL1 knockout mice, cisplatin model, RNA-seq, Western blot, immunofluorescence, in vitro podocyte cisplatin treatment, transmission electron microscopy for mitochondria Molecular medicine Medium 37875838
2016 Noradrenaline induces CX3CL1 protein and mRNA accumulation in primary cortical neurons and increases soluble CX3CL1 levels independent of ADAM10/ADAM17 activity. Noradrenaline-treated neurons showed enhanced dendritic arborization with CX3CL1 accumulating at dendritic bifurcations. The soluble CX3CL1 produced reduced nitrite accumulation in microglia, demonstrating a noradrenaline→neuronal CX3CL1→microglial anti-inflammatory signaling pathway. Primary cortical neuron cultures, ADAM10/ADAM17 inhibitors, RT-PCR, Western blot, ELISA for soluble CX3CL1, nitrite accumulation assay in microglia, immunofluorescence for dendritic morphology Neuropharmacology Medium 27923568
2019 IFN-γ and IL-1β or TNF-α synergistically upregulate CX3CL1 expression in first-trimester decidual cells via MEK1/2, JNK, and NF-κB signaling pathways; specific inhibitors of each pathway suppressed CX3CL1 production. CX3CL1 elicited concentration-dependent enhancement of CD56brightCD16- NK cell migration in chemotaxis assays. Primary human first-trimester decidual cell cultures, cytokine stimulation, MEK1/2/JNK/NF-κB pharmacological inhibitors, ELISA, qRT-PCR, NK cell chemotaxis assay Reproductive sciences Medium 30606080
2022 CX3CL1 promotes M1 macrophage polarization and osteoclast differentiation through the NF-κB signaling pathway in ankylosing spondylitis; NF-κB inhibitor BAY-117082 prevented M1 polarization and osteoclast differentiation, and anti-CX3CL1 monoclonal antibody alleviated disease in AS model mice. In vitro macrophage polarization assays, osteoclast differentiation assays, NF-κB inhibitor, anti-CX3CL1 neutralizing antibody, AS mouse model, histological assessment Journal of translational medicine Medium 37626378
2021 CX3CL1-CX3CR1 signaling deficiency (Cx3cr1 knockout or Cx3cl1 knockdown) exacerbates obesity-induced adipose tissue inflammation and insulin resistance by reducing M2-polarized macrophage migration and causing M1-dominant shift in epididymal white adipose tissue. Bone marrow transplantation from Cx3cr1-/- donors was sufficient to impair glucose tolerance and insulin sensitivity; in vivo Cx3cl1 administration attenuated glucose intolerance. Cx3cr1 knockout mice, bone marrow transplantation, high-fat diet and leptin-deficient mouse models, flow cytometry, glucose tolerance and insulin tolerance tests Endocrinology Medium 33765141
2024 CX3CL1 release is specifically associated with immunogenic apoptosis (induced by mitoxantrone) but not ferroptosis or accidental necrosis. Addition of recombinant CX3CL1 to non-immunogenic apoptotic cancer cells in a prophylactic tumor vaccination model induced a robust anti-tumor immune response and improved mouse survival, demonstrating that CX3CL1 functions as a 'find me' signal enhancing immunogenicity of apoptosis. Luminex multiplex cytokine quantification, murine fibrosarcoma and melanoma cell lines, prophylactic vaccination mouse tumor model, comparison across death modalities Frontiers in immunology Medium 39011040

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
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
2002 Expression of fractalkine (CX3CL1) and its receptor, CX3CR1, during acute and chronic inflammation in the rodent CNS. Glia 202 11870871
2014 Modulating neurotoxicity through CX3CL1/CX3CR1 signaling. Frontiers in cellular neuroscience 187 25152714
2021 CX3CL1/CX3CR1 signaling targets for the treatment of neurodegenerative diseases. Pharmacology & therapeutics 144 34492237
2004 Regulation of CX3CL1/fractalkine expression in endothelial cells. Journal of atherosclerosis and thrombosis 128 15067194
2013 Chemokines and atherosclerosis: focus on the CX3CL1/CX3CR1 pathway. Acta pharmacologica Sinica 109 23974513
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
2005 CX3CL1 (fractalkine) and CX3CR1 expression in myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis: kinetics and cellular origin. Journal of neuroinflammation 98 16053521
2010 CCL2/CCR2 and CX3CL1/CX3CR1 chemokine axes and their possible involvement in age-related macular degeneration. Journal of neuroinflammation 95 21126357
2020 Fractalkine/CX3CL1 in Neoplastic Processes. International journal of molecular sciences 93 32466280
2021 Regulation and biological functions of the CX3CL1-CX3CR1 axis and its relevance in solid cancer: A mini-review. Journal of Cancer 87 33391453
2020 MicroRNA-195 prevents hippocampal microglial/macrophage polarization towards the M1 phenotype induced by chronic brain hypoperfusion through regulating CX3CL1/CX3CR1 signaling. Journal of neuroinflammation 84 32819407
2007 Sequential processing of the transmembrane chemokines CX3CL1 and CXCL16 by alpha- and gamma-secretases. Biochemical and biophysical research communications 82 17467666
2010 Role of CX3CR1/CX3CL1 axis in primary and secondary involvement of the nervous system by cancer. Journal of neuroimmunology 81 20630606
2022 CX3CL1/CX3CR1 interaction protects against lipotoxicity-induced nonalcoholic steatohepatitis by regulating macrophage migration and M1/M2 status. Metabolism: clinical and experimental 76 35914622
2019 CX3CL1-CX3CR1 interaction mediates macrophage-mesothelial cross talk and promotes peritoneal fibrosis. Kidney international 75 30948201
2002 Fractalkine (CX3CL1) and brain inflammation: Implications for HIV-1-associated dementia. Journal of neurovirology 75 12476352
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
2010 CX3CR1/CX3CL1 axis negatively controls glioma cell invasion and is modulated by transforming growth factor-β1. Neuro-oncology 68 20511186
2014 Role of fractalkine/CX3CL1 and its receptor in the pathogenesis of inflammatory and malignant diseases with emphasis on B cell malignancies. Mediators of inflammation 65 24799766
2012 Altered expression of CX3CL1 in patients with epilepsy and in a rat model. The American journal of pathology 65 22464888
2020 CX3CL1 Signaling in the Tumor Microenvironment. Advances in experimental medicine and biology 64 32060841
2008 CX3CL1 and CCL14 regulate extracellular matrix and adhesion molecules in the trophoblast: potential roles in human embryo implantation. Biology of reproduction 64 18367676
2021 Fractalkine (CX3CL1) and Its Receptor CX3CR1: A Promising Therapeutic Target in Chronic Kidney Disease? Frontiers in immunology 62 34163473
2014 The chemokine CX3CL1 (fractalkine) and its receptor CX3CR1: occurrence and potential role in osteoarthritis. Archivum immunologiae et therapiae experimentalis 61 24556958
2018 CX3CL1/fractalkine enhances prostate cancer spinal metastasis by activating the Src/FAK pathway. International journal of oncology 60 30066854
2016 CX3CL1/CX3CR1 in Alzheimer's Disease: A Target for Neuroprotection. BioMed research international 59 27429982
2022 CX3CL1 inhibits NLRP3 inflammasome-induced microglial pyroptosis and improves neuronal function in mice with experimentally-induced ischemic stroke. Life sciences 56 35461837
2020 Fractalkine (CX3CL1) signaling and neuroinflammation in Parkinson's disease: Potential clinical and therapeutic implications. Pharmacological research 55 32445958
2016 Fractalkine/CX3CL1 in rheumatoid arthritis. Modern rheumatology 55 27484962
2023 CX3CL1 promotes M1 macrophage polarization and osteoclast differentiation through NF-κB signaling pathway in ankylosing spondylitis in vitro. Journal of translational medicine 51 37626378
2019 Crosstalk between the CX3CL1/CX3CR1 Axis and Inflammatory Signaling Pathways in Tissue Injury. Current protein & peptide science 51 30843484
2020 Two forms of CX3CL1 display differential activity and rescue cognitive deficits in CX3CL1 knockout mice. Journal of neuroinflammation 50 32410624
2016 Therapeutic intervention of inflammatory/immune diseases by inhibition of the fractalkine (CX3CL1)-CX3CR1 pathway. Inflammation and regeneration 48 29259682
2019 Soluble CX3CL1 gene therapy improves cone survival and function in mouse models of retinitis pigmentosa. Proceedings of the National Academy of Sciences of the United States of America 47 31036641
2019 CX3CL1 promotes lung cancer cell migration and invasion via the Src/focal adhesion kinase signaling pathway. Oncology reports 46 30628679
2019 Tenophages: a novel macrophage-like tendon cell population expressing CX3CL1 and CX3CR1. Disease models & mechanisms 44 31744815
2017 CX3CL1/CX3CR1 Axis, as the Therapeutic Potential in Renal Diseases: Friend or Foe? Current gene therapy 44 29446734
2014 CX₃CL1 (fractalkine) and its receptor CX₃CR1 regulate atopic dermatitis by controlling effector T cell retention in inflamed skin. The Journal of experimental medicine 43 24821910
2021 Regulation and function of CX3CR1 and its ligand CX3CL1 in kidney disease. Cell and tissue research 42 34009468
2013 Fractalkine (CX3CL1) and its receptor CX3CR1 may contribute to increased angiogenesis in diabetic placenta. Mediators of inflammation 42 23956503
2024 CX3CL1 (Fractalkine)-CX3CR1 Axis in Inflammation-Induced Angiogenesis and Tumorigenesis. International journal of molecular sciences 40 38731899
2019 Activated CX3CL1/Smad2 Signals Prevent Neuronal Loss and Alzheimer's Tau Pathology-Mediated Cognitive Dysfunction. The Journal of neuroscience : the official journal of the Society for Neuroscience 40 31822518
2018 CD200-, CX3CL1-, and TREM2-mediated neuron-microglia interactions and their involvements in Alzheimer's disease. Reviews in the neurosciences 40 29729150
2007 Increased expression of fractalkine (CX3CL1) and its receptor, CX3CR1, in Wegener's granulomatosis--possible role in vascular inflammation. Rheumatology (Oxford, England) 38 17616549
2021 Human CD16+ monocytes promote a pro-atherosclerotic endothelial cell phenotype via CX3CR1-CX3CL1 interaction. Cardiovascular research 37 32717023
2013 CX3CL1 and CX3CR1 expression in tertiary lymphoid structures in salivary gland infiltrates: fractalkine contribution to lymphoid neogenesis in Sjogren's syndrome. Rheumatology (Oxford, England) 37 24324211
2024 Neuronal cathepsin S increases neuroinflammation and causes cognitive decline via CX3CL1-CX3CR1 axis and JAK2-STAT3 pathway in aging and Alzheimer's disease. Aging cell 35 39453382
2020 ADAM17-regulated CX3CL1 expression produced by bone marrow endothelial cells promotes spinal metastasis from hepatocellular carcinoma. International journal of oncology 35 32319605
2019 The intracellular domain of CX3CL1 regulates adult neurogenesis and Alzheimer's amyloid pathology. The Journal of experimental medicine 35 31209068
2008 Thrombin-induced expression of endothelial CX3CL1 potentiates monocyte CCL2 production and transendothelial migration. Journal of leukocyte biology 34 18436581
2021 CX3CL1-CX3CR1 Signaling Deficiency Exacerbates Obesity-induced Inflammation and Insulin Resistance in Male Mice. Endocrinology 33 33765141
2011 Fractalkine/CX3CL1 protects striatal neurons from synergistic morphine and HIV-1 Tat-induced dendritic losses and death. Molecular neurodegeneration 33 22093090
2014 CX3CL1/CX3CR1 and CCL2/CCR2 chemokine/chemokine receptor complex in patients with AMD. PloS one 31 25503251
2012 Arterial and venous endothelia display differential functional fractalkine (CX3CL1) expression by angiotensin-II. Arteriosclerosis, thrombosis, and vascular biology 31 23117657
2023 CX3CL1 Pathway as a Molecular Target for Treatment Strategies in Alzheimer's Disease. International journal of molecular sciences 30 37175935
2006 Expression and targeting of CX3CL1 (fractalkine) in renal tubular epithelial cells. Journal of the American Society of Nephrology : JASN 30 17151328
2003 The chemokine CX3CL1 regulates NK cell activity in vivo. Cellular immunology 30 14698146
2020 CX3CL1 and IL-15 Promote CD8 T cell chemoattraction in HIV and in atherosclerosis. PLoS pathogens 29 32976527
2019 Role of CX3CL1/CX3CR1 Signaling Axis Activity in Osteoporosis. Mediators of inflammation 29 31780870
2024 YTHDF2 in peritumoral hepatocytes mediates chemotherapy-induced antitumor immune responses through CX3CL1-mediated CD8+ T cell recruitment. Molecular cancer 28 39237909
2023 Targeted inhibition of CX3CL1 limits podocytes ferroptosis to ameliorate cisplatin-induced acute kidney injury. Molecular medicine (Cambridge, Mass.) 28 37875838
2022 Structure and Function of Ligand CX3CL1 and its Receptor CX3CR1 in Cancer. Current medicinal chemistry 28 35770395
2018 CX3CL1-Fc treatment prevents atherosclerosis in Ldlr KO mice. Molecular metabolism 28 30553772
2013 Interaction between CX3CL1 and CX3CR1 regulates vasculitis induced by immune complex deposition. The American journal of pathology 28 23470165
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
2023 The Cytokine CX3CL1 and ADAMs/MMPs in Concerted Cross-Talk Influencing Neurodegenerative Diseases. International journal of molecular sciences 26 37175729
2020 Platelets are recruited to hepatocellular carcinoma tissues in a CX3CL1-CX3CR1 dependent manner and induce tumour cell apoptosis. Molecular oncology 26 32799418
2017 Shear Stress Counteracts Endothelial CX3CL1 Induction and Monocytic Cell Adhesion. Mediators of inflammation 26 28522896
2016 Expression of Chemokine XCL2 and CX3CL1 in Lung Cancer. Medical science monitor : international medical journal of experimental and clinical research 26 27156946
2015 Chemokine CX3CL1 and its receptor CX3CR1 are associated with human atherosclerotic lesion volnerability. Thrombosis research 26 25845619
2012 ERK pathway and sheddases play an essential role in ethanol-induced CX3CL1 release in pancreatic stellate cells. Laboratory investigation; a journal of technical methods and pathology 26 23147224
2008 Glial cross-talk by transmembrane chemokines CX3CL1 and CXCL16. Journal of neuroimmunology 26 18538418
2003 Human keratinocytes express fractalkine/CX3CL1. Journal of dermatological science 26 12727021
2021 Potential biomarkers reflecting inflammation in patients with severe periodontitis: Fractalkine (CX3CL1) and its receptor (CX3CR1). Journal of periodontal research 24 33641164
2019 Endothelial expression of fractalkine (CX3CL1) is induced by Toll-like receptor 3 signaling in cultured human glomerular endothelial cells. Modern rheumatology 24 31625434
2016 The role of CX3CL1 in fetal-maternal interaction during human gestation. Cell adhesion & migration 24 26745855
2006 The CX3CL1-CX3CR1 system and psoriasis. Experimental dermatology 24 17002687
2024 Direct interaction of platelet with tumor cell aggravates hepatocellular carcinoma metastasis by activating TLR4/ADAM10/CX3CL1 axis. Cancer letters 23 38280480
2023 Pathophysiological impact of CXC and CX3CL1 chemokines in preeclampsia and gestational diabetes mellitus. Frontiers in cell and developmental biology 23 37928902
2022 CX3CL1 promotes cell sensitivity to ferroptosis and is associated with the tumor microenvironment in clear cell renal cell carcinoma. BMC cancer 23 36397015
2019 Regulation of CX3CL1 Expression in Human First-Trimester Decidual Cells: Implications for Preeclampsia. Reproductive sciences (Thousand Oaks, Calif.) 23 30606080
2012 CX3CL1 expression in the conjunctiva is involved in immune cell trafficking during toxic ocular surface inflammation. Mucosal immunology 23 22692452
2019 Placental CX3CL1 is Deregulated by Angiotensin II and Contributes to a Pro-Inflammatory Trophoblast-Monocyte Interaction. International journal of molecular sciences 22 30717334
2003 Expression of CX3CL1/fractalkine by mesangial cells in vitro and in acute anti-Thy1 glomerulonephritis in rats. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 22 14605272
2018 CX3CL1/CX3CR1 Axis Contributes to Angiotensin II-Induced Vascular Smooth Muscle Cell Proliferation and Inflammatory Cytokine Production. Inflammation 21 29356931
2017 Naringin Protects Against High Glucose-Induced Human Endothelial Cell Injury Via Antioxidation and CX3CL1 Downregulation. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 21 28848146
2020 CX3CL1 homo-oligomerization drives cell-to-cell adherence. Scientific reports 20 32494000
2012 The transmembrane chemokines CXCL16 and CX3CL1 and their receptors are expressed in human meningiomas. Oncology reports 20 23229614
2024 Mild Hypoxia Accelerates Cerebral Cavernous Malformation Disease Through CX3CR1-CX3CL1 Signaling. Arteriosclerosis, thrombosis, and vascular biology 19 38660801
2024 PVT1 promotes proliferation and macrophage immunosuppressive polarization through STAT1 and CX3CL1 regulation in glioblastoma multiforme. CNS neuroscience & therapeutics 18 38287522
2019 Cocaine-induced changes in CX3CL1 and inflammatory signaling pathways in the hippocampus: Association with IL1β. Neuropharmacology 18 31704270
2022 CX3CL1 Worsens Cardiorenal Dysfunction and Serves as a Therapeutic Target of Canagliflozin for Cardiorenal Syndrome. Frontiers in pharmacology 17 35370759
2021 Ursodeoxycholic acid impairs liver-infiltrating T-cell chemotaxis through IFN-γ and CX3CL1 production in primary biliary cholangitis. European journal of immunology 17 33710617
2012 CX3CL1/fractalkine is a novel regulator of normal and malignant human B cell function. Journal of leukocyte biology 17 22457367
2024 CX3CL1 release during immunogenic apoptosis is associated with enhanced anti-tumour immunity. Frontiers in immunology 16 39011040
2021 STAT3/miR-15a-5p/CX3CL1 Loop Regulates Proliferation and Migration of Vascular Endothelial Cells in Atherosclerosis. International journal of medical sciences 16 33456354
2016 Noradrenaline induces CX3CL1 production and release by neurons. Neuropharmacology 16 27923568

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