Affinage

CXCR3

C-X-C chemokine receptor type 3 · UniProt P49682

Length
368 aa
Mass
40.7 kDa
Annotated
2026-04-28
100 papers in source corpus 23 papers cited in narrative 23 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CXCR3 is a Gαi-coupled chemokine receptor that directs leukocyte trafficking, neuronal excitability, and cell fate decisions by transducing signals from its cognate ligands CXCL9, CXCL10, and CXCL11 through ligand-specific phosphorylation barcodes that differentially engage G proteins and β-arrestins from both the plasma membrane and endosomes (PMID:37030291, PMID:36195635). The receptor couples to RhoA/Rac1-dependent actin reorganization, p38/ERK MAPK cascades, Akt, and STAT3 to drive chemotaxis, integrin-mediated adhesion, and transcriptional reprogramming in T cells, NK cells, macrophages, fibroblasts, and neurons (PMID:11571298, PMID:30401786, PMID:33196963, PMID:36610561). Two major splice variants, CXCR3-A and CXCR3-B, mediate opposing proliferative/migratory versus growth-suppressive responses, and additional biased signaling arises from ligand identity—CXCL11 preferentially promotes IL-10-producing Tr1 cells while CXCL9/CXCL10 favor Th1/Th17 effector differentiation (PMID:18832436, PMID:26657511, PMID:16337473). CXCR3 forms functional heteromers with CXCR4 that alter ligand binding and β-arrestin2 recruitment, adding a further layer of signal diversification (PMID:23170857).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1998 High

    Establishing the basic pharmacology of CXCR3 resolved which chemokines activate the receptor and with what affinity, defining it as a high-affinity receptor for IP-10/CXCL10 and MIG/CXCL9 that signals through G-protein coupling on activated T cells.

    Evidence Radioligand binding, calcium mobilization, and chemotaxis in transfected cells and primary activated T cells

    PMID:9660793

    Open questions at the time
    • Downstream signaling pathways beyond calcium not yet mapped
    • CXCL11 not yet characterized as a ligand
    • Splice variant biology unknown
  2. 1999 High

    Demonstrating hierarchical cross-desensitization among CXCL9, CXCL10, and CXCL11 at murine CXCR3 established that the three ligands engage distinct receptor conformations, prefiguring the concept of ligand bias at this receptor.

    Evidence Binding, calcium flux, chemotaxis, and cross-desensitization in CXCR3-transfected L1.2 cells

    PMID:10556837

    Open questions at the time
    • Molecular basis of conformational selectivity unknown
    • No structural information on receptor–ligand interface
  3. 2001 High

    Identification of RhoA, Rac1, and p38/ERK MAPK as downstream effectors of CXCR3 linked receptor activation to actin cytoskeleton reorganization, integrin modulation, and cell migration, providing the first mechanistic framework for CXCR3-driven chemotaxis.

    Evidence GTPase pull-down, actin polymerization, integrin adhesion, and MAPK Western blot in human melanoma cells

    PMID:11571298

    Open questions at the time
    • Whether these pathways operate identically in leukocytes versus cancer cells
    • Contribution of β-arrestin signaling not addressed
  4. 2002 High

    Structure–function dissection of CXCR3 ligands identified the chemokine N-terminus as essential for receptor activation (versus binding), enabling design of the first truncation-based CXCR3 antagonist and providing a molecular map of the ligand–receptor interface.

    Evidence Hybrid chemokine mutagenesis with binding, calcium, chemotaxis, and internalization readouts; NMR structure of CXCL10 with CXCR3 N-terminal peptide

    PMID:12173928 PMID:12417585

    Open questions at the time
    • No full-length receptor structure
    • Structural basis for differential ligand potency not resolved
  5. 2004 High

    Discovery that CXCR3-A and CXCR3-B splice variants are co-expressed on non-hematopoietic cells and that CXCR3 on melanoma cells drives metastasis established that isoform balance controls cell behavior beyond immune cell trafficking.

    Evidence Splice-variant RT-PCR in airway epithelial cells; antisense knockdown of CXCR3 on B16F10 melanoma with in vivo metastasis reduction

    PMID:15155273 PMID:15173015

    Open questions at the time
    • Distinct signaling cascades downstream of each isoform not yet defined
    • No isoform-selective pharmacological tools
  6. 2005 Medium

    Showing that CXCL10 (via CXCR3-A) and CXCL4 (via CXCR3-B) drive opposing Th1 versus Th2 transcriptional programs through T-bet and GATA-3 demonstrated that CXCR3 isoforms transduce qualitatively different signals controlling T cell differentiation.

    Evidence qRT-PCR, ELISA, promoter assays, and anti-CXCR3 neutralization in human T cells

    PMID:16337473

    Open questions at the time
    • Signal transduction intermediates linking each isoform to transcription factor activation uncharacterized
    • Single-lab finding
  7. 2008 Medium

    Demonstrating that calcineurin inhibitors selectively downregulate CXCR3-B while sparing CXCR3-A, thereby shifting renal cancer cells toward proliferation via Gαi signaling, provided direct evidence that isoform ratio governs the net growth-suppressive versus proliferative output.

    Evidence qRT-PCR, proliferation/migration assays, pertussis toxin Gi-blockade, in vivo tumor growth in renal cancer cells

    PMID:18832436

    Open questions at the time
    • Mechanism by which calcineurin inhibitors selectively regulate CXCR3-B transcription unclear
    • Relevance to other cancer types not tested
  8. 2011 High

    Two discoveries—CXCL4 as a biased CXCR3 agonist that activates Akt/ERK without inducing migration, and CXCR3-driven fibroblast invasion via MMP-1—expanded the receptor's functional repertoire beyond T cell chemotaxis to biased signaling and tissue-destructive invasion.

    Evidence Calcium, phospho-Western, chemotaxis in human T cells (CXCL4 bias); Matrigel invasion, MMP-1, antibody/AMG487 blockade in synovial fibroblasts

    PMID:21255008 PMID:21811993

    Open questions at the time
    • Structural basis for CXCL4-specific signaling bias unknown
    • Role of β-arrestin in fibroblast invasion not examined
  9. 2013 High

    Identification of CXCR3–CXCR4 heteromers that alter ligand binding and β-arrestin2 recruitment revealed that CXCR3 function is modulated by receptor–receptor interactions, providing a mechanism for context-dependent signal integration.

    Evidence Co-IP, TR-FRET, saturation BRET, GPCR-HIT, competitive binding, β-arrestin2 recruitment in HEK293T cells

    PMID:23170857

    Open questions at the time
    • Physiological relevance of heteromers in primary immune cells not demonstrated
    • No structural model of the heteromer interface
  10. 2015 High

    Genetic evidence in mice and zebrafish that CXCL11–CXCR3 signaling selectively drives Tr1 cell development and macrophage recruitment to infection sites established ligand-specific immunological outcomes in vivo, distinguishing CXCL11 from CXCL9/CXCL10.

    Evidence Transgenic/KO mouse T cell differentiation assays; zebrafish cxcr3.2 mutant with live macrophage imaging and recombinant ligand rescue

    PMID:25573892 PMID:26657511

    Open questions at the time
    • Intracellular transducers mediating CXCL11-specific Tr1 programming not identified
    • Evolutionary conservation of ligand bias between fish and mammals assumed but not formally proven
  11. 2017 High

    Linking CXCR3 to mitochondrial dynamics—regulation of DRP1, FIS1, and MFN1 expression, membrane potential, and ROS production—revealed a non-canonical effector arm of CXCR3 signaling in hepatocytes during NASH.

    Evidence CXCR3 KO mice, pharmacological inhibitors, siRNA in hepatocyte lines, TEM, mitochondrial functional assays

    PMID:29158819

    Open questions at the time
    • Direct signaling intermediates between CXCR3 and mitochondrial fission/fusion gene regulation unknown
    • Whether this pathway operates in immune cells not tested
  12. 2018 High

    Pharmacological separation of G protein– versus β-arrestin–biased CXCR3 signaling in vivo demonstrated that β-arrestin bias drives T cell migration via Akt activation while G protein bias does not, establishing the functional significance of biased agonism at CXCR3 for inflammation.

    Evidence Biased small-molecule agonists, mouse contact hypersensitivity, phospho-Akt, human T cell chemotaxis

    PMID:30401786

    Open questions at the time
    • Whether β-arrestin bias operates through CXCR3-A, -B, or both not resolved
    • Structural basis for agonist-directed bias not available
  13. 2019 High

    Two studies extended CXCR3 function to integrin-dependent cardiac T cell infiltration and sensory neuron-mediated itch, showing that the receptor controls tissue-specific immune cell entry and directly modulates neuronal signaling.

    Evidence CXCR3 KO mice in pressure-overload cardiac remodeling with shear-flow adhesion assay; neutrophil depletion and CXCR3 antagonism in atopic dermatitis itch model

    PMID:30779709 PMID:31631836

    Open questions at the time
    • Specific CXCR3 signaling pathway in sensory neurons controlling itch not fully delineated
    • Relative contribution of CXCR3 ligands in cardiac fibroblasts not dissected
  14. 2020 High

    Electrophysiological demonstration that CXCR3 on DRG neurons enhances excitability via p38/ERK, and that CXCR3 directs NK cell repositioning within splenic compartments, extended the receptor's roles to nociception and spatial immune regulation within lymphoid tissues.

    Evidence CXCR3 KO and shRNA in DRG neurons with action potential recording and behavioral pain tests; CXCR3 KO with splenic imaging and adoptive transfer during LCMV infection

    PMID:33196963 PMID:34314390

    Open questions at the time
    • Ion channel targets of p38/ERK downstream of CXCR3 in neurons not identified
    • Whether NK cell repositioning requires β-arrestin or G protein signaling not tested
  15. 2022 High

    Resolving that CXCR3 generates distinct signaling outputs at the plasma membrane versus endosomes—and that β-arrestin-biased inflammation requires receptor internalization—established subcellular location as a third axis of signal diversification alongside ligand identity and splice variant.

    Evidence BRET-based subcellular signaling sensors, internalization blockade, mouse contact hypersensitivity, RNA-seq of CD8+ T cells

    PMID:36195635

    Open questions at the time
    • Endosomal signaling machinery interacting with CXCR3 not identified
    • Whether location bias differs among the three endogenous ligands not fully resolved
  16. 2023 High

    Mass spectrometry-based identification of ligand-specific CXCR3 phosphorylation barcodes, with mutagenesis showing phosphosite-specific control of β-arrestin2 conformation and T cell chemotaxis, provided the molecular code underlying biased agonism at this receptor.

    Evidence Global phosphoproteomics, site-directed mutagenesis, BRET-based β-arrestin2 conformational sensors, MD simulations, T cell chemotaxis

    PMID:37030291

    Open questions at the time
    • Which kinases (GRKs) write each barcode not determined
    • Whether phosphobarcodes differ in primary human T cell subtypes not tested
  17. 2023 Medium

    Identification of CXCR3→STAT3→SLC7A11 suppression→ferroptosis as a neuronal death pathway in epilepsy expanded CXCR3 effector biology to include regulation of redox homeostasis and programmed cell death beyond immune contexts.

    Evidence Epileptic mouse model, astrocyte-neuron co-culture, STAT3/SLC7A11/GPX4 pathway analysis, ferroptosis inhibitors, epileptic patient brain tissue

    PMID:36610561

    Open questions at the time
    • Whether this ferroptotic pathway is CXCR3-A or CXCR3-B specific unknown
    • Independent replication in a second epilepsy model lacking
    • Contribution of other CXCR3 ligands besides CXCL10 not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Critical open questions include which GRK isoforms write each ligand-specific phosphorylation barcode, the structural basis for CXCR3–CXCR4 heteromer formation, and how subcellular location bias integrates with splice variant identity to produce cell-type-specific functional outcomes in vivo.
  • No full-length cryo-EM structure of CXCR3 in complex with endogenous ligands
  • GRK identity for each phosphobarcode unknown
  • Integration of splice variant, ligand bias, and location bias in a single quantitative framework lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 6
Localization
GO:0005886 plasma membrane 3 GO:0005768 endosome 1
Pathway
R-HSA-162582 Signal Transduction 8 R-HSA-168256 Immune System 5
Partners
ARRB2CXCL10CXCL11CXCL4CXCL9CXCR4
Complex memberships
CXCR3-CXCR4 heteromer

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 CXCR3, when heterologously expressed, binds IP-10 (CXCL10) and MIG (CXCL9) with Ki values of 0.14 nM and 4.9 nM respectively; the receptor signals through G-protein coupling and has similar pharmacological properties on endogenous receptor expressed on activated T cells. Eotaxin was identified as a natural CXCR3 antagonist that blocks IP-10-mediated receptor activation without itself activating the receptor. Radioligand binding assays, receptor transfection, calcium mobilization assays, chemotaxis assays The Journal of biological chemistry High 9660793
1999 Murine CXCR3 binds IP-10, ITAC, and Mig with distinct affinities (Kd ~1.35, 1.41, and 11.65 nM respectively) and induces chemotaxis, intracellular calcium flux, and cross-desensitization in a hierarchical manner (ITAC > Mig > IP-10), suggesting ligands interact with different receptor conformational isoforms to produce divergent responses. Ligand binding assays on transfected pre-B lymphocyte line (L1.2), calcium mobilization, chemotaxis assays, cross-desensitization experiments European journal of immunology High 10556837
2001 CXCR3 on human melanoma cells (BLM line) is functional: CXCL9 (Mig) activation leads to RhoA and Rac1 small GTPase activation, actin cytoskeleton reorganization, cell chemotaxis, and modulation of integrin VLA-5- and VLA-4-dependent adhesion to fibronectin. CXCR3 and CXCR4 ligands also activate MAPKs p44/42 and p38 on these cells. GTPase pull-down assays, actin polymerization assays, chemotaxis assays, integrin adhesion assays, MAPK activation (Western blot) The Journal of biological chemistry High 11571298
2002 Structure-function analysis of CXCR3 ligands showed that CXCL11 (I-TAC) is the most potent agonist; NH2-terminal truncation of I-TAC (removing first 3 residues) converts it to a pan-CXCR3 antagonist that blocks ligand binding, migration, Ca2+ responses, and receptor internalization. The NH2-terminus and N-loop region (residues 1–8 and 12–17) of I-TAC confer higher activity compared to IP-10. The extended basic COOH-terminal region of Mig (absent in I-TAC and IP-10) is important for Mig binding and activity. Competitive binding assays, calcium flux assays, chemotaxis assays, receptor internalization assays, hybrid chemokine construction and mutagenesis The Journal of biological chemistry High 12417585
2002 NMR structure of IP-10 (CXCL10) revealed an unusual structural feature potentially explaining its ability to bind both CXCR3 and CCR3. The surface of IP-10 interacting with the N-terminus of CXCR3 was mapped to a hydrophobic cleft formed by the N-loop and 40s-loop region, with an additional interaction involving the N-terminus and 30s-loop of IP-10. NMR spectroscopy, NMR chemical shift perturbation upon addition of CXCR3 N-terminal peptide Biochemistry High 12173928
2004 CXCR3 is constitutively expressed by human airway epithelial cells (HAEC) as both CXCR3-A and CXCR3-B splice variants (~78,000 receptors/cell), and CXCR3 ligands induce chemotactic responses and actin reorganization in these cells, indicating functional autocrine CXCR3 signaling in structural airway cells. RT-PCR, expression arrays, flow cytometry, immunofluorescence, competitive radioligand displacement binding, chemotaxis assays, actin reorganization assays American journal of physiology. Lung cellular and molecular physiology High 15155273
2004 CXCR3 expression on B16F10 melanoma cells mediates CXCL9/CXCL10/CXCL11-induced actin polymerization, migration, invasion, and cell survival in vitro; antisense-mediated reduction of CXCR3 expression reduced lymph node metastasis to ~15% of control in syngeneic hosts. Elevated CXCL9/CXCL10 in lymph nodes increased metastatic frequency in a CXCR3-dependent manner. Antisense RNA knockdown, in vitro actin polymerization, migration and invasion assays, in vivo syngeneic transplantation, antibody blockade of CXCR3 ligands Cancer research High 15173015
2005 CXCL10 and CXCL4 exert opposite effects on Th1/Th2 cytokine production via CXCR3: CXCL10 (acting via CXCR3-A) upregulates IFN-γ and downregulates IL-4/IL-5/IL-13, while CXCL4 (acting via CXCR3-B) does the opposite. These effects involve distinct signal transduction pathways and differential regulation of T-bet and GATA-3 transcription factors, and CXCL4 (but not CXCL10) directly activates IL-5 and IL-13 promoters. qRT-PCR, flow cytometry, ELISA, anti-CXCR3 antibody neutralization, promoter activation assays The Journal of allergy and clinical immunology Medium 16337473
2008 Calcineurin inhibitors (CNI) downregulate CXCR3-B expression without affecting CXCR3-A, thereby promoting renal cancer cell proliferation and migration via Gi protein signaling through CXCR3-A; this identifies CXCR3-A as promoting cell proliferation while CXCR3-B inhibits cell growth, and demonstrates that isoform balance controls cancer cell behavior. qRT-PCR, cell proliferation and migration assays, Gi protein inhibition with pertussis toxin, in vivo tumor growth assessment Journal of the American Society of Nephrology Medium 18832436
2011 CXCL10/CXCR3 axis controls synovial fibroblast invasion: CXCR3 blockade (anti-CXCR3 antibody or AMG487) reduced invasiveness of fibroblast-like synoviocytes by up to 77%, decreased MMP-1 by 65%, inhibited intracellular calcium influx (64–100%), and blocked actin cytoskeleton reorganization and lamellipodia formation in both rat arthritis and human RA FLS. Matrigel invasion assay, anti-CXCR3 antibody blockade, pharmacological inhibition (AMG487), MMP production measurement, calcium influx measurement, actin cytoskeleton imaging Arthritis and rheumatism High 21811993
2011 CXCL4 activates CXCR3 in human T lymphocytes inducing intracellular calcium mobilization and Akt and p44/p42 ERK phosphorylation via Gαi protein (pertussis toxin-sensitive), but unlike other CXCR3 agonists, fails to elicit migratory responses and does not induce surface CXCR3 downregulation, demonstrating biased signaling at CXCR3. Calcium mobilization assays, phospho-Western blot (Akt, ERK), pertussis toxin treatment, chemotaxis assay, flow cytometric surface receptor quantification Immunology High 21255008
2013 CXCR3 and CXCR4 form heteromeric complexes in HEK293T cells (confirmed by co-immunoprecipitation, TR-FRET, saturation BRET, and GPCR-HIT). Chemokine binding to the two receptors is mutually exclusive on co-expressing membranes. The small CXCR3 agonist VUF10661 impairs CXCL12 binding to CXCR4. CXCR3-CXCR4 heteromers specifically recruit β-arrestin2 in response to agonist stimulation. Co-immunoprecipitation, TR-FRET, saturation BRET, GPCR-HIT (heteromer identification technology), competitive radioligand binding, β-arrestin2 recruitment assay British journal of pharmacology High 23170857
2015 CXCL11, with higher binding affinity to CXCR3, drives development of IL-10-high T regulatory 1 (Tr1) cells and activates a different signaling cascade than CXCL9/CXCL10, which promote effector Th1/Th17 cells — demonstrating ligand-biased signaling at CXCR3 that controls distinct CD4+ T cell subset development. Transgenic and knockout mouse models, flow cytometry, cytokine measurement, T cell differentiation assays Journal of leukocyte biology Medium 26657511
2015 CXCR3-CXCL11 signaling axis mediates macrophage recruitment to bacterial infection sites: zebrafish cxcr3.2 mutants show attenuated macrophage chemotaxis to bacterial infections but not to infection-independent stimuli; CXCL11-like chemokines are the functional ligands of Cxcr3.2 (demonstrated by recombinant protein chemoattraction assay). Cxcr3.2 deficiency also limits macrophage-mediated dissemination of Mycobacterium marinum and granuloma formation. Zebrafish cxcr3.2 mutant (loss-of-function), pharmacological CXCR3 antagonism (NBI74330), recombinant ligand in vivo administration, live imaging of macrophage migration, bacterial burden quantification Disease models & mechanisms High 25573892
2017 CXCR3 promotes mitochondrial dysfunction in hepatocytes during NASH development: CXCR3 knockout or pharmacological inhibition (SCH546738, AMG487) restored mitochondrial membrane potential, ATP content, and reduced mitochondrial ROS accumulation and DNA damage. CXCR3 regulates DRP1 and FIS1 (fission proteins) and MFN1 (fusion protein) expression, and CXCR3 knockdown by siRNA in AML-12 and HepG2 cells diminished mitochondrial dysfunction. CXCR3 knockout mice, pharmacological inhibition, siRNA knockdown in hepatocyte lines, transmission electron microscopy, mitochondrial membrane potential, ATP, ROS, and DNA damage assays, Western blot for mitochondrial dynamics proteins Theranostics High 29158819
2018 Biased agonists of CXCR3 differentially activate G protein- vs. β-arrestin-mediated signaling pathways. In a mouse contact hypersensitivity model, β-arrestin-biased (but not G protein-biased) CXCR3 agonist potentiated inflammation and increased T cell recruitment. β-arrestin-biased CXCR3 signaling activated Akt kinase to promote T cell migration, while G protein-biased signaling did not. Small-molecule biased agonist characterization, mouse contact hypersensitivity model, flow cytometry, phosphoprotein analysis (Akt), human T cell chemotaxis assays Science signaling High 30401786
2019 CXCR3-mediated Th1 cell adhesion to ICAM-1 under shear conditions promotes CD4+ T cell infiltration into the heart during pressure overload. Cardiac fibroblasts and myeloid cells are the source of CXCL9 and CXCL10. Genetic deletion of CXCR3 disrupts CD4+ T cell heart infiltration and prevents adverse cardiac remodeling. CXCR3 knockout mice, flow cytometry, cardiac function measurements (echocardiography), shear flow T cell adhesion assay to ICAM-1, histological analysis of fibrosis JCI insight High 30779709
2019 Neutrophils are required for induction of CXCL10 in atopic dermatitis, which activates CXCR3 on sensory neurons to promote itch. CXCR3 antagonism attenuated chronic itch in a mouse model of atopic dermatitis. Neutrophil depletion in mouse AD model, CXCR3 antagonist treatment, behavioral scratch assays, gene expression analysis eLife Medium 31631836
2020 CXCL10 activates CXCR3 on DRG neurons to enhance neuronal excitability via p38 and ERK activation, contributing to neuropathic pain maintenance. CXCR3 knockout abolishes CXCL10-induced action potential increases in DRG neurons. Intra-DRG Cxcr3 shRNA attenuated SNL-induced mechanical allodynia and heat hyperalgesia. CXCR3 knockout mice, Cxcr3 shRNA knockdown, in vitro electrophysiology (action potential recording), p38/ERK phosphorylation assays, behavioral pain testing Neuroscience bulletin High 33196963
2020 CXCR3 is required for NK cell redistribution from marginal zones into T cell-rich regions of the spleen during LCMV infection, enabling perforin-dependent NK cell suppression of CD4+ T cells. This redistribution is driven by type I IFN-dependent upregulation of CXCR3 ligands. CXCR3 knockout mice, lymphoid tissue immunofluorescence, flow cytometry, LCMV infection model, adoptive transfer experiments The Journal of clinical investigation High 34314390
2022 Differential subcellular CXCR3 signaling contributes to biased agonism: CXCR3 signaling profile changes as it traffics from plasma membrane to endosomes in a ligand-specific manner. Endosomal signaling is critical for biased activation of G proteins, β-arrestins, and ERK. In a mouse contact hypersensitivity model, β-arrestin-biased CXCR3-mediated inflammation requires receptor internalization. Live-cell imaging, BRET-based subcellular signaling assays, internalization blockade, mouse contact hypersensitivity model, RNA-seq transcriptional profiling of CD8+ T cells Nature communications High 36195635
2023 Different CXCR3 chemokines (CXCL9, CXCL10, CXCL11) generate distinct CXCR3 phosphorylation barcodes (identified by mass spectrometry) associated with differential transducer activation. Mutation of CXCR3 phosphosites altered β-arrestin 2 conformation and chemotactic profiles of T cells in an agonist- and phosphosite-specific manner. Mass spectrometry-based global phosphoproteomics, site-directed mutagenesis of CXCR3 phosphosites, BRET-based β-arrestin 2 conformational assays, molecular dynamics simulations, T cell chemotaxis assays Cell chemical biology High 37030291
2023 A1 astrocyte-secreted CXCL10 activates CXCR3 on neurons to enhance STAT3 phosphorylation and suppress SLC7A11, leading to GPX4-dependent ferroptosis and lipid peroxidation in epilepsy. Epileptic mouse model, astrocyte-neuron co-culture, CXCR3-dependent signaling pathway analysis (STAT3 phosphorylation, SLC7A11, GPX4), ferroptosis inhibitors, histological analysis of epileptic patient brain tissue Free radical biology & medicine Medium 36610561

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2017 CXCL9, CXCL10, CXCL11/CXCR3 axis for immune activation - A target for novel cancer therapy. Cancer treatment reviews 1157 29207310
2011 CXCR3 in T cell function. Experimental cell research 788 21376175
2011 CXCR3 ligands: redundant, collaborative and antagonistic functions. Immunology and cell biology 774 21221121
2001 Differential expression of CXCR3 targeting chemokines CXCL10, CXCL9, and CXCL11 in different types of skin inflammation. The Journal of pathology 289 11523046
2014 CXCR3 ligands in disease and therapy. Cytokine & growth factor reviews 239 25498524
2004 Pivotal role of CXCR3 in melanoma cell metastasis to lymph nodes. Cancer research 232 15173015
2020 CXCR3 Ligands in Cancer and Autoimmunity, Chemoattraction of Effector T Cells, and Beyond. Frontiers in immunology 220 32547545
2007 Chemokine receptor CXCR3 promotes colon cancer metastasis to lymph nodes. Oncogene 204 17297455
2001 Expression of functional chemokine receptors CXCR3 and CXCR4 on human melanoma cells. The Journal of biological chemistry 200 11571298
2002 Expression of the chemokine receptors CCR4, CCR5, and CXCR3 by human tissue-infiltrating lymphocytes. The American journal of pathology 195 11786428
2005 Regulation of CXCR3 and CXCR4 expression during terminal differentiation of memory B cells into plasma cells. Blood 190 15687242
1998 Binding and functional properties of recombinant and endogenous CXCR3 chemokine receptors. The Journal of biological chemistry 165 9660793
2018 CXCL9, CXCL10, CXCL11, and their receptor (CXCR3) in neuroinflammation and neurodegeneration. Advances in clinical and experimental medicine : official organ Wroclaw Medical University 161 29893515
2002 Structure-function relationship between the human chemokine receptor CXCR3 and its ligands. The Journal of biological chemistry 154 12417585
2019 Neutrophils promote CXCR3-dependent itch in the development of atopic dermatitis. eLife 138 31631836
2018 The Role of CXCR3 and Its Chemokine Ligands in Skin Disease and Cancer. Frontiers in medicine 138 30320116
2013 CXCR3, a double-edged sword in tumor progression and angiogenesis. Biochimica et biophysica acta 133 23994549
1999 The chemokine receptor CXCR3 is expressed on malignant B cells and mediates chemotaxis. The Journal of clinical investigation 123 10393705
2012 The role of CXCR3 and CXCR4 in colorectal cancer metastasis. International journal of cancer 119 22689289
2005 Chemokine receptor CXCR3: an unexpected enigma. Current topics in developmental biology 118 16124999
2002 The CXCR3 binding chemokine IP-10/CXCL10: structure and receptor interactions. Biochemistry 113 12173928
2015 The CXCR3-CXCL11 signaling axis mediates macrophage recruitment and dissemination of mycobacterial infection. Disease models & mechanisms 109 25573892
2009 The chemokine receptors CXCR4 and CXCR3 in cancer. Current oncology reports 92 19216844
2007 CXCR3 axis: role in inflammatory bowel disease and its therapeutic implication. Endocrine, metabolic & immune disorders drug targets 91 17584151
2005 CXCR3-mediated opposite effects of CXCL10 and CXCL4 on TH1 or TH2 cytokine production. The Journal of allergy and clinical immunology 91 16337473
2000 IL-4 enhances keratinocyte expression of CXCR3 agonistic chemokines. Journal of immunology (Baltimore, Md. : 1950) 90 10903743
2009 Antagonism of chemokine receptor CXCR3 inhibits osteosarcoma metastasis to lungs. International journal of cancer 88 19544560
2019 The Distinct Roles of CXCR3 Variants and Their Ligands in the Tumor Microenvironment. Cells 84 31216755
2022 The role of CXCR3 and its ligands in cancer. Frontiers in oncology 81 36479091
2019 CXCR3 regulates CD4+ T cell cardiotropism in pressure overload-induced cardiac dysfunction. JCI insight 78 30779709
2011 Expression and agonist responsiveness of CXCR3 variants in human T lymphocytes. Immunology 78 21255008
2011 CXCL10 and its receptor CXCR3 regulate synovial fibroblast invasion in rheumatoid arthritis. Arthritis and rheumatism 78 21811993
1999 Structure and function of the murine chemokine receptor CXCR3. European journal of immunology 78 10556837
2015 Biased signaling pathways via CXCR3 control the development and function of CD4+ T cell subsets. Journal of leukocyte biology 77 26657511
2017 Pro-Inflammatory CXCR3 Impairs Mitochondrial Function in Experimental Non-Alcoholic Steatohepatitis. Theranostics 75 29158819
2001 Chemokine receptor CXCR3 expression in inflammatory bowel disease. Inflammatory bowel diseases 73 11720316
2016 Emerging importance of chemokine receptor CXCR3 and its ligands in cardiovascular diseases. Clinical science (London, England : 1979) 71 26888559
2016 CXCR3 Blockade Inhibits T Cell Migration into the Skin and Prevents Development of Alopecia Areata. Journal of immunology (Baltimore, Md. : 1950) 71 27412416
2010 CXCR3 binding chemokine and TNFSF14 over expression in bladder urothelium of patients with ulcerative interstitial cystitis. The Journal of urology 71 20096889
2008 Towards small-molecule CXCR3 ligands with clinical potential. ChemMedChem 68 18442035
2010 Chemokine receptor CXCR3 promotes growth of glioma. Carcinogenesis 66 21051441
2015 CXCR3 in carcinoma progression. Histology and histopathology 65 25663474
2005 Clinical significance of CXCR3 and CXCR4 expression in primary melanoma. International journal of cancer 63 15981210
2023 Neurotoxic A1 astrocytes promote neuronal ferroptosis via CXCL10/CXCR3 axis in epilepsy. Free radical biology & medicine 61 36610561
2004 The chemokine receptor CXCR3 and its splice variant are expressed in human airway epithelial cells. American journal of physiology. Lung cellular and molecular physiology 61 15155273
2016 Enhanced monocyte migration to CXCR3 and CCR5 chemokines in COPD. The European respiratory journal 60 26965295
2013 Identification and profiling of CXCR3-CXCR4 chemokine receptor heteromer complexes. British journal of pharmacology 58 23170857
2008 Combined CXCR3/CCR5 blockade attenuates acute and chronic rejection. Journal of immunology (Baltimore, Md. : 1950) 56 18354195
2009 Identification of migR, a regulatory element of the Francisella tularensis live vaccine strain iglABCD virulence operon required for normal replication and trafficking in macrophages. Infection and immunity 55 19349423
2020 CXCL10/CXCR3 Signaling in the DRG Exacerbates Neuropathic Pain in Mice. Neuroscience bulletin 54 33196963
2007 Targeting of Th1-associated chemokine receptors CXCR3 and CCR5 as therapeutic strategy for inflammatory diseases. Mini reviews in medicinal chemistry 53 18045212
2015 Small Molecule CXCR3 Antagonists. Journal of medicinal chemistry 52 26535614
2014 The role of CXCR3 in DSS-induced colitis. PloS one 52 24992040
2017 CXCR3.1 and CXCR3.2 Differentially Contribute to Macrophage Polarization in Teleost Fish. Journal of immunology (Baltimore, Md. : 1950) 51 28500070
2017 Chemokine Receptor CXCR3 in the Spinal Cord Contributes to Chronic Itch in Mice. Neuroscience bulletin 50 28401489
2019 Targeting of CXCR3 improves anti-myeloma efficacy of adoptively transferred activated natural killer cells. Journal for immunotherapy of cancer 48 31699153
2006 CXCR3 and its ligands in a murine model of obliterative bronchiolitis: regulation and function. Journal of immunology (Baltimore, Md. : 1950) 46 16709871
2003 Roles of CCR2 and CXCR3 in the T cell-mediated response occurring during lupus flares. Arthritis and rheumatism 43 14673999
2023 Interferon-γ production by Tfh cells is required for CXCR3+ pre-memory B cell differentiation and subsequent lung-resident memory B cell responses. Immunity 42 37699392
2022 Location bias contributes to functionally selective responses of biased CXCR3 agonists. Nature communications 42 36195635
2019 The Role of CXCR3 in Neurological Diseases. Current neuropharmacology 42 29119926
2014 CXCR3 modulates obesity-induced visceral adipose inflammation and systemic insulin resistance. Obesity (Silver Spring, Md.) 42 24124129
2008 Calcineurin inhibitors modulate CXCR3 splice variant expression and mediate renal cancer progression. Journal of the American Society of Nephrology : JASN 41 18832436
2007 A small-molecule compound targeting CCR5 and CXCR3 prevents airway hyperresponsiveness and inflammation. The European respiratory journal 41 18094012
2018 Biased agonists of the chemokine receptor CXCR3 differentially control chemotaxis and inflammation. Science signaling 40 30401786
2021 Natural killer cell immunosuppressive function requires CXCR3-dependent redistribution within lymphoid tissues. The Journal of clinical investigation 38 34314390
2020 Chemokine receptor CXCR3 is required for lethal brain pathology but not pathogen clearance during cryptococcal meningoencephalitis. Science advances 37 32596454
2018 Differential role of CXCR3 in inflammation and colorectal cancer. Oncotarget 37 29707158
2016 Andrographolide inhibits prostate cancer by targeting cell cycle regulators, CXCR3 and CXCR7 chemokine receptors. Cell cycle (Georgetown, Tex.) 37 27029529
2016 Increased CXCR3 Expression of Infiltrating Plasma Cells in Hunner Type Interstitial Cystitis. Scientific reports 37 27339056
2014 The association of CXCR3 and renal cell carcinoma metastasis. The Journal of urology 37 24518777
2001 Expression pattern of CXCR3, CXCR4, and CCR3 chemokine receptors in the developing human brain. Journal of neuropathology and experimental neurology 37 11202173
2023 PD-1highCXCR5-CD4+ peripheral helper T cells promote CXCR3+ plasmablasts in human acute viral infection. Cell reports 35 36596303
2016 TNF-α augments CXCR2 and CXCR3 to promote progression of renal cell carcinoma. Journal of cellular and molecular medicine 35 27297979
2020 Tumor inhibition or tumor promotion? The duplicity of CXCR3 in cancer. Journal of leukocyte biology 34 32745326
2015 Treg-cell depletion promotes chemokine production and accumulation of CXCR3(+) conventional T cells in intestinal tumors. European journal of immunology 33 25754875
2011 CXCR3 enhances a T-cell-dependent epidermal proliferative response and promotes skin tumorigenesis. Cancer research 33 21734014
2016 Dual Roles for CXCL4 Chemokines and CXCR3 in Angiogenesis and Invasion of Pancreatic Cancer. Cancer research 32 27634764
2003 CXCR3 chemokine receptor-plasma IP10 interaction in patients with coronary artery disease. Circulation journal : official journal of the Japanese Circulation Society 32 14578618
2021 Dual role for CXCR3 and CCR5 in asthmatic type 1 inflammation. The Journal of allergy and clinical immunology 31 34146578
2016 Pancreatic β-Cell production of CXCR3 ligands precedes diabetes onset. BioFactors (Oxford, England) 29 27325565
2014 CXCR3 controls T-cell accumulation in fat inflammation. Arteriosclerosis, thrombosis, and vascular biology 29 24812325
2013 Dichotomy of CCL21 and CXCR3 in nerve injury-evoked and autoimmunity-evoked hyperalgesia. Brain, behavior, and immunity 29 23643685
2012 The Beginning of the End: CXCR3 Signaling in Late-Stage Wound Healing. Advances in wound care 29 24527313
2006 Expression of the chemokine receptor CXCR3 in human renal allografts--a prospective study. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 29 16421159
2020 Effective Treatments for Bladder Cancer Affecting CXCL9/CXCL10/CXCL11/CXCR3 Axis: A Review. Oman medical journal 28 32181005
2015 CXCR3 Polymorphism and Expression Associate with Spontaneous Preterm Birth. Journal of immunology (Baltimore, Md. : 1950) 28 26209629
2017 Hepatocellular carcinoma and CXCR3 chemokines: a narrative review. La Clinica terapeutica 27 28240761
2014 CXCR3⁺CCR5⁺ T cells and autoimmune diseases: guilty as charged? The Journal of clinical investigation 27 25180533
2020 Cxcl9l and Cxcr3.2 regulate recruitment of osteoclast progenitors to bone matrix in a medaka osteoporosis model. Proceedings of the National Academy of Sciences of the United States of America 26 32719141
2023 Phosphorylation barcodes direct biased chemokine signaling at CXCR3. Cell chemical biology 25 37030291
2021 CXCL10 and CXCR3 in the Trigeminal Ganglion Contribute to Trigeminal Neuropathic Pain in Mice. Journal of pain research 24 33469355
2019 The Chemokine Receptor CXCR3 Isoform B Drives Breast Cancer Stem Cells. Breast cancer : basic and clinical research 23 31619923
2006 CXCR3 and IFN protein-10 in Pneumocystis pneumonia. Journal of immunology (Baltimore, Md. : 1950) 23 16849496
2024 CXCR3-Expressing T Cells in Infections and Autoimmunity. Frontiers in bioscience (Landmark edition) 22 39206903
2014 Crosstalk between TGF-β1 and CXCR3 signaling during urethral fibrosis. Molecular and cellular biochemistry 22 24907118
2018 Anticonvulsant agent DPP4 inhibitor sitagliptin downregulates CXCR3/RAGE pathway on seizure models. Experimental neurology 21 29885296
2008 CXCR3-B expression correlates with tumor necrosis extension in renal cell carcinoma. The Journal of urology 21 19095263
2024 Phosphatidylserine-incorporated exosome mimetics encapsulating CXCR3 antagonist alleviate osteoporosis. Advanced functional materials 20 39539387
2003 CCR3 and CXCR3 as drug targets for allergy: principles and potential. Current drug targets. Inflammation and allergy 20 14561176