Affinage

CXCR3

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

Length
368 aa
Mass
40.7 kDa
Annotated
2026-06-09
100 papers in source corpus 27 papers cited in narrative 27 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CXCR3 is a Gαi-coupled chemokine receptor that controls the trafficking of effector lymphocytes, NK cells, regulatory T cells, and myeloid cells into inflammatory, infectious, tumor, and lymphoid compartments (PMID:17538187, PMID:25751061, PMID:30779709, PMID:34314390). It binds the interferon-inducible chemokines CXCL10 (IP-10), CXCL9 (MIG), and CXCL11 (I-TAC) with distinct affinities and signals through intracellular calcium mobilization and chemotaxis, while eotaxin acts as a natural antagonist (PMID:9660793, PMID:10556837). Ligand engagement couples to small GTPases (RhoA, Rac1) and MAPK cascades to drive actin cytoskeleton reorganization, integrin-dependent adhesion, and directed migration (PMID:11571298, PMID:30779709). The receptor exhibits pronounced ligand bias: the three endogenous chemokines impose distinct phosphorylation barcodes that shape β-arrestin 2 conformation and produce agonist-specific transducer activation and chemotactic outputs (PMID:37030291), with β-arrestin-biased agonism—rather than G protein-biased agonism—driving T cell chemotaxis via Akt and potentiating inflammation in vivo (PMID:30401786). This bias is spatially encoded: as CXCR3 internalizes, endosomal signaling becomes critical for biased G protein, β-arrestin, and ERK activation, and CXCR3 also assembles Gαi:β-arrestin complexes that couple to the clathrin adaptor AP-2 (PMID:36195635, PMID:35316095). Two splice variants exert opposing effects—CXCR3-A promotes motility and invasion via PLCβ3/calpain, whereas CXCR3-B suppresses migration through cAMP (PMID:22236567). Transcription of CXCR3 is repressed by TGFβ through Smad2 binding to its promoter, limiting CD8+ T cell tumor infiltration (PMID:32273499). Beyond immune-cell trafficking, CXCR3 is functionally expressed on glia, neurons, fibroblasts, and tumor cells, where it drives synovial fibroblast invasion via MMP-1 (PMID:21811993), mediates neuropathic pain and itch through neuronal p38/ERK (PMID:33196963, PMID:25932692), promotes neuronal ferroptosis via a STAT3–SLC7A11–GPX4 axis (PMID:36610561), and forms negatively cooperative heteromers with CXCR4 (PMID:23170857).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1998 High

    Establishing which chemokines CXCR3 binds and with what affinity defined the receptor's ligand repertoire and pharmacology.

    Evidence Radioligand competition binding and functional activation on transfected cells and activated T cells

    PMID:9660793

    Open questions at the time
    • Did not address signaling consequences downstream of binding
    • Eotaxin antagonism mechanism not structurally defined
  2. 1999 High

    Adding CXCL11 to the ligand set and ranking chemotactic potency suggested that different ligands engage distinct receptor conformations—an early hint of biased signaling.

    Evidence Radioligand binding, calcium flux, chemotaxis, and cross-desensitization on transfected L1.2 cells (murine ortholog)

    PMID:10556837

    Open questions at the time
    • Conformational states inferred functionally, not structurally resolved
    • No transducer-level dissection
  3. 1999 Medium

    Functional CXCR3 on malignant B cells, mediating chemotaxis without calcium flux, showed the receptor operates beyond canonical T cell biology and can signal through non-calcium routes.

    Evidence Flow cytometry, antibody-blocked chemotaxis, and calcium assays on CLL B cells

    PMID:10393705

    Open questions at the time
    • Mechanism of calcium-independent chemotaxis unresolved
    • Single lab
  4. 2001 Medium

    Identifying RhoA/Rac1, actin remodeling, integrin modulation, and MAPK activation linked CXCR3 ligand binding to the cytoskeletal and adhesion machinery underlying migration.

    Evidence GTPase, actin imaging, adhesion, and MAPK assays in melanoma cell lines

    PMID:11571298

    Open questions at the time
    • No receptor mutagenesis
    • Tumor cell context may not generalize to leukocytes
  5. 2007 High

    Genetic knockout established that CXCR3's in vivo role is specifically effector T cell trafficking to inflamed tissue, not systemic priming.

    Evidence CXCR3-/- mice in nephrotoxic nephritis with trafficking vs. immunity readouts

    PMID:17538187

    Open questions at the time
    • Did not distinguish ligand contributions
    • Receptor signaling mechanism in vivo not addressed
  6. 2011 Medium

    CXCL4 signaling via CXCR3 that triggers calcium/Akt/ERK but not migration provided direct evidence for functional selectivity among CXCR3 ligands.

    Evidence Calcium, Akt/ERK phosphorylation, pertussis toxin, chemotaxis, and internalization assays in human T lymphocytes

    PMID:21255008

    Open questions at the time
    • CXCL4 acts via CXCR3-B variant—isoform attribution incomplete
    • Structural basis of bias unknown
  7. 2011 Medium

    Demonstrating CXCL10/CXCR3-driven fibroblast invasion via MMP-1 and actin remodeling extended CXCR3 function to tissue-destructive stromal cells in arthritis.

    Evidence Matrigel invasion, antibody/AMG487 blockade, MMP and calcium assays in rat and human FLS

    PMID:21811993

    Open questions at the time
    • Isoform involved not defined
    • Single lab
  8. 2012 Medium

    Isoform-specific manipulation showed CXCR3-A and CXCR3-B exert opposing effects on migration via distinct effectors (PLCβ3/calpain vs cAMP), explaining context-dependent CXCR3 outputs.

    Evidence Isoform overexpression/knockdown with migration and pathway readouts in prostate cancer cells

    PMID:22236567

    Open questions at the time
    • Structural basis of opposing signaling not defined
    • Single lab
  9. 2013 High

    Identifying CXCR3-CXCR4 heteromers with negative binding cooperativity revealed cross-regulation between chemokine receptors.

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

    PMID:23170857

    Open questions at the time
    • Physiological relevance in primary cells not shown
    • Heteromer stoichiometry unresolved
  10. 2018 High

    Distinguishing β-arrestin-biased from G protein-biased agonism showed β-arrestin signaling specifically drives chemotaxis via Akt and amplifies inflammation in vivo.

    Evidence Biased small-molecule agonists, transducer/chemotaxis/Akt assays, mouse contact hypersensitivity, and patient biopsies

    PMID:30401786

    Open questions at the time
    • Did not resolve how barcodes select transducers
    • Endosomal contribution not yet defined
  11. 2022 High

    Subcellular biosensors established location bias—endosomal signaling after internalization is critical for biased G protein, β-arrestin, and ERK activation in vivo.

    Evidence Subcellular BRET sensors, internalization assays, compartmentalized ERK readouts, and mouse CHS model with internalization blockade

    PMID:36195635

    Open questions at the time
    • Trafficking determinants on receptor incompletely mapped
    • Ligand-specific endosomal kinetics not fully resolved
  12. 2022 Medium

    Characterizing Gαi:β-arrestin complexes that couple to AP-2 but not ERK showed these complexes are a distinct, context-dependent signaling species at CXCR3.

    Evidence Complex formation, G protein, β-arrestin, ERK, and AP-2 interaction assays with biased agonists

    PMID:35316095

    Open questions at the time
    • Functional downstream output of AP-2 coupling unclear
    • Single lab
  13. 2023 High

    Mass spectrometry phosphoproteomics defined ligand-specific phosphorylation barcodes and tied specific phosphosites to β-arrestin conformation and chemotactic outcome—providing a molecular code for bias.

    Evidence Phosphoproteomics, phosphosite mutagenesis, β-arrestin 2 conformational biosensors, molecular dynamics, and T cell chemotaxis

    PMID:37030291

    Open questions at the time
    • Kinases generating each barcode not identified
    • Endogenous in vivo barcode dynamics not measured
  14. 2020 High

    ChIP evidence that TGFβ/Smad2 represses the CXCR3 promoter defined a transcriptional brake controlling CD8+ T cell trafficking into tumors.

    Evidence CD8-specific ALK5 conditional knockout, tumor models, Smad2 ChIP, migration assays, and in vivo CXCR3 blockade

    PMID:32273499

    Open questions at the time
    • Other transcriptional regulators not mapped
    • Isoform-specific regulation not addressed
  15. 2015 High

    A series of in vivo studies established CXCR3 as a master controller of distinct leukocyte trafficking programs—effector and regulatory T cells, NK cells, and macrophages—to inflamed, infected, and lymphoid tissues.

    Evidence CXCR3-/- mice and antibody/antagonist blockade across nephritis, cardiac pressure overload, decidual Listeria infection, Treg recruitment, NK relocation in LCMV, and zebrafish mycobacterial models

    PMID:23656737 PMID:25573892 PMID:25751061 PMID:30779709 PMID:34314390

    Open questions at the time
    • Ligand-specific contributions to each trafficking program not fully separated
    • Role of biased signaling in vivo not resolved across all contexts
  16. 2020 Medium

    Defining neuronal CXCR3 signaling through p38/ERK in DRG neurons and a STAT3-SLC7A11-GPX4 ferroptosis axis extended CXCR3 function to neuronal excitability, pain, itch, and neurodegeneration.

    Evidence Spinal nerve ligation, intra-DRG shRNA, electrophysiology, CXCR3-/- mice, p38 inhibition, CHS itch behavior, and epilepsy co-culture/ferroptosis assays

    PMID:25932692 PMID:33196963 PMID:36610561

    Open questions at the time
    • Receptor isoform in neurons not defined
    • Connection between trafficking-canonical and neuronal signaling unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How specific receptor kinases generate each ligand-defined phosphorylation barcode, and how barcode plus subcellular location are jointly decoded into distinct physiological trafficking and signaling outcomes in vivo, remains unresolved.
  • Kinases responsible for individual barcodes unidentified
  • No structural model linking phosphosite patterns to transducer selection
  • In vivo relevance of Gαi:β-arrestin/AP-2 complexes unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 3
Localization
GO:0005768 endosome 2 GO:0005886 plasma membrane 2
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-168256 Immune System 4
Partners
AP-2ARRB2CXCL10CXCL11CXCL4CXCL9CXCR4
Complex memberships
CXCR3-CXCR4 heteromer

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 CXCR3 binds IP10 (CXCL10) and MIG (CXCL9) with Ki values of 0.14 nM and 4.9 nM, respectively, when heterologously expressed; the endogenous receptor on activated T cells has similar pharmacology. CXCR3 has very modest affinity for SDF-1α and little or no affinity for other CXC chemokines. Eotaxin competes for IP10 binding with moderate affinity but does not activate CXCR3, acting instead as a natural antagonist. Radioligand competition binding assays on transfected cells and activated T cells; functional receptor activation assays The Journal of biological chemistry High 9660793
1999 Murine CXCR3 binds ITAC (CXCL11), IP10 (CXCL10), and MIG (CXCL9) with Kd values of ~1.35, ~1.35, and ~11.65 nM, respectively. All three ligands induce chemotaxis and intracellular calcium elevation. The hierarchy of potency for chemotaxis and cross-desensitization is ITAC > IP10 = MIG, suggesting the ligands interact with different receptor conformational states to produce divergent responses. Radioligand binding on transfected L1.2 cells; calcium flux assays; chemotaxis assays; cross-desensitization experiments European journal of immunology High 10556837
2001 CXCR3 expressed on human melanoma cells is functional: the ligand MIG (CXCL9) activates RhoA and Rac1 small GTPases, induces actin cytoskeleton reorganization, triggers cell chemotaxis, and modulates VLA-5- and VLA-4-dependent adhesion to fibronectin. MIG and SDF-1α also activate MAPKs p44/42 and p38 in these cells. GTPase activation assays; actin cytoskeleton imaging; chemotaxis assays; integrin adhesion assays; MAPK phosphorylation assays in melanoma cell lines The Journal of biological chemistry Medium 11571298
1999 CXCR3 is expressed on malignant B cells from chronic lymphocytic leukemia (CLL) patients but not on normal B cells; CXCR3 on CLL B cells is a fully functional receptor mediating chemotaxis toward IP-10 and MIG, and this migration is blocked by anti-CXCR3 antibody. Notably, IP-10 and MIG did not induce cytosolic calcium changes in these malignant B cells. Flow cytometry; chemotaxis assays with blocking antibody; calcium flux assays The Journal of clinical investigation Medium 10393705
2002 CXCR3 is functionally expressed on cultured mouse and human astrocytes and microglia; stimulation with CXCR3 ligands induces intracellular calcium transients and chemotaxis in these glial cells, demonstrating that neuronal-derived CXCR3 ligands can signal to endogenous CNS cells. RT-PCR; in situ hybridization; immunocytochemistry; calcium flux assays; chemotaxis assays in primary glial cultures Neuroscience Medium 12074892
2007 CXCR3 mediates T cell recruitment to the inflamed kidney: CXCR3-deficient mice show significantly reduced renal T cell infiltrates and develop less severe nephrotoxic nephritis (lower albuminuria, better renal function, reduced glomerular crescent formation) despite mounting an equivalent systemic immune response, indicating the defect is specifically in effector T cell trafficking rather than priming. CXCR3-/- knockout mouse model; nephrotoxic nephritis induction; histology; flow cytometry; renal function assays; antigen-specific IgG and IFN-γ measurements Journal of the American Society of Nephrology High 17538187
2011 CXCL10/CXCR3 signaling drives synovial fibroblast invasion in rheumatoid arthritis: CXCL10 treatment increases fibroblast invasiveness through Matrigel, an effect blocked by anti-CXCR3 antibody or the antagonist AMG487. CXCR3 blockade reduces MMP-1 production by 65%, inhibits intracellular calcium influx, and disrupts actin cytoskeleton reorganization and lamellipodia formation. In vitro Matrigel invasion assay; CXCR3 antibody blockade; AMG487 pharmacological inhibition; MMP production measurement; calcium influx assay; actin cytoskeleton imaging in rat and human FLS Arthritis and rheumatism Medium 21811993
2011 CXCL4 activates CXCR3-mediated intracellular calcium mobilization and phosphorylation of Akt and p44/p42 ERK in activated human T lymphocytes, with signaling sensitive to pertussis toxin (indicating Gαi coupling). However, CXCL4 fails to elicit migratory responses and does not cause loss of CXCR3 surface expression, unlike classical CXCR3-A agonists—indicating functional selectivity/ligand bias. Calcium mobilization assays; Akt and ERK phosphorylation assays; pertussis toxin inhibition; chemotaxis assays; flow cytometry for receptor internalization in human T lymphocytes Immunology Medium 21255008
2012 CXCR3-A and CXCR3-B splice variants have opposing functions in prostate cancer cells: CXCR3-A promotes cell motility and invasiveness via PLCβ3 and μ-calpain activation, whereas CXCR3-B suppresses migration via cAMP upregulation and m-calpain inhibition. Overexpression of CXCR3-B in invasive DU-145 cells decreases cell movement and invasion. CXCR3 isoform-specific overexpression and knockdown; cell migration and invasion assays; PLCβ3, calpain and cAMP pathway measurement in human prostate cancer cell lines Molecular cancer Medium 22236567
2013 CXCR3 and CXCR4 form heteromeric complexes in HEK293T cells, as demonstrated by co-immunoprecipitation, time-resolved FRET, saturation BRET, and GPCR-HIT assay. Within these heteromers, chemokine binding is mutually exclusive on membranes; the CXCR3 agonist VUF10661 impairs CXCL12 binding to CXCR4. The heteromers support specific β-arrestin2 recruitment upon agonist stimulation. Co-immunoprecipitation; TR-FRET; saturation BRET; GPCR-HIT assay; equilibrium competition binding; β-arrestin2 recruitment assay in HEK293T cells British journal of pharmacology High 23170857
2015 The CXCR3-CXCL11 signaling axis mediates macrophage chemotaxis to sites of mycobacterial infection in zebrafish: cxcr3.2 mutant embryos show attenuated macrophage recruitment to bacterial foci, mimicked by the CXCR3 antagonist NBI74330. Two infection-inducible CXCL11-like chemokines are functional ligands of Cxcr3.2 in vivo. Cxcr3.2 deficiency limits macrophage-mediated mycobacterial dissemination and granuloma formation. Zebrafish cxcr3.2 mutant; pharmacological antagonism (NBI74330); recombinant chemokine injection in vivo; live imaging; bacterial burden quantification Disease models & mechanisms Medium 25573892
2015 CXCR3 on CXCL9-producing neutrophil/macrophage-recruited maternal CD8+ T cells mediates their decidual infiltration leading to fetal wastage after Listeria monocytogenes infection; CXCR3 blockade or genetic deficiency extinguishes decidual T cell accumulation and prevents fetal resorption, even when initiated after infection. CXCR3-/- mice; CXCR3 neutralizing antibody; Listeria infection model; flow cytometry; adoptive transfer of fetal-specific T cells The Journal of clinical investigation High 25751061
2015 Biased CXCR3 agonists differentially activate G protein vs. β-arrestin signaling: β-arrestin-biased agonism (but not G protein-biased agonism) drives T cell chemotaxis via Akt activation in mouse and human T cells and potentiates allergic contact hypersensitivity inflammation in vivo. CXCR3 and β-arrestin are co-expressed in T cells at inflamed sites. Small-molecule biased agonist characterization; G protein and β-arrestin signaling assays; chemotaxis assays; Akt phosphorylation assays; mouse contact hypersensitivity model; patient biopsy immunostaining Science signaling High 30401786
2015 CXCR3 on CD8+ T cells is required for CXCR3+ regulatory T cell migration into sites of Th1-type inflammation; CXCR3-deficient mice show prolonged contact hypersensitivity due to reduced Treg infiltration and decreased TGF-β and IL-10 at late time points; adoptive transfer of CXCR3+ Tregs into CXCR3-/- mice normalizes the response. CXCR3-/- mice; contact hypersensitivity model; flow cytometry; cytokine measurement; adoptive Treg transfer Journal of immunology Medium 23656737
2019 CXCR3 on CD4+ Th1 cells is required for their recruitment into the heart during pressure overload: cardiac fibroblasts and myeloid cells are the source of CXCL9 and CXCL10; these chemokines promote Th1 cell adhesion to ICAM-1 under shear conditions in a CXCR3-dependent manner. Genetic deletion of CXCR3 disrupts CD4+ T cell cardiac infiltration and prevents adverse cardiac remodeling. CXCR3-/- mice; pressure overload (transverse aortic constriction) model; flow cytometry; in vitro adhesion assay under shear; identification of cellular chemokine source by cell-type isolation JCI insight High 30779709
2020 TGFβ suppresses CD8+ T cell expression of CXCR3 by promoting Smad2 binding to the CXCR3 promoter; ALK5 (TGFβ receptor I)-deficient CD8+ T cells show increased CXCR3 expression, enhanced migration toward CXCL10, and greater tumor infiltration. In vivo CXCR3 blockade partially abrogates the survival advantage of ALK5ΔCD8 mice. CD8-specific ALK5 conditional knockout mice; tumor models; ChIP (Smad2 binding to CXCR3 promoter); migration assays; CXCR3 blocking antibody in vivo; flow cytometry Nature communications High 32273499
2022 Differential subcellular signaling (location bias) contributes to biased agonism at CXCR3: the receptor's 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 vivo, β-arrestin-biased CXCR3-mediated inflammation depends on receptor internalization. Subcellular BRET sensors; receptor internalization assays; ERK signaling compartmentalization assays; mouse contact hypersensitivity model with internalization-blocking approaches; CD8+ T cell transcriptomics Nature communications High 36195635
2023 CXCR3 chemokines (CXCL9, CXCL10, CXCL11) generate distinct phosphorylation barcodes at CXCR3 as revealed by mass spectrometry-based global phosphoproteomics; these barcodes are associated with differential transducer activation. Mutation of specific CXCR3 phosphosites alters β-arrestin 2 conformation (cellular assays and molecular dynamics) and produces agonist- and receptor-specific chemotactic profiles in T cells. Mass spectrometry phosphoproteomics; site-directed mutagenesis of CXCR3 phosphosites; β-arrestin 2 conformational biosensors; molecular dynamics simulations; T cell chemotaxis assays Cell chemical biology High 37030291
2022 Biased CXCR3 agonists differentially form Gαi:β-arrestin complexes; formation of these complexes does not correlate with either G protein activation or β-arrestin recruitment. Gαi:β-arrestin complexes at CXCR3 couple to clathrin adaptor AP-2 but not to ERK (unlike at V2 vasopressin receptor), indicating context-dependent signaling by these complexes. Gαi:β-arrestin complex formation assays; G protein activation assays; β-arrestin recruitment assays; ERK signaling assays; AP-2 interaction assays with biased small-molecule and endogenous agonists Science signaling Medium 35316095
2017 CXCR3 ablation protects against NASH development by preserving mitochondrial function: CXCR3 knockout or pharmacological inhibition reduces mitochondrial ROS, DNA damage, and loss of membrane potential/ATP; CXCR3 loss normalizes DRP1 and FIS1 (fission proteins) and MFN1 (fusion protein) expression; siCXCR3 in hepatocytes similarly diminishes mitochondrial dysfunction. CXCR3-/- knockout mice; CXCR3 antagonists (SCH546738, AMG487); siRNA knockdown in hepatocyte cell lines; transmission electron microscopy; mitochondrial ROS, ATP, membrane potential assays; Western blot for DRP1, FIS1, MFN1 Theranostics Medium 29158819
2020 CXCL10/CXCR3 signaling in dorsal root ganglion (DRG) neurons exacerbates neuropathic pain: spinal nerve ligation increases CXCR3 in DRG neurons; intra-DRG Cxcr3 shRNA attenuates mechanical allodynia and heat hyperalgesia; CXCL10 increases DRG neuron action potential firing via CXCR3, activating p38 and ERK; p38 inhibition reduces CXCL10-induced neuronal excitability. In Cxcr3-/- mice, CXCL10 fails to increase action potentials. Spinal nerve ligation model; intra-DRG shRNA injection; electrophysiology (action potential recording); CXCR3-/- mice; p38 inhibitor (SB203580); p38 and ERK phosphorylation assays in DRG neurons and ND7-23 neuronal cells Neuroscience bulletin Medium 33196963
2015 CXCR3 signaling in sensory neurons mediates allergic itch: CXCL10 directly activates a subset of cutaneous DRG neurons via neuronal CXCR3; a CXCR3 antagonist attenuates spontaneous itch-like behaviors in CHS mice; intradermal CXCL10 elicits itch-like but not pain-like behaviors in CHS mice but not controls. CXCR3 mRNA, protein and signaling activity are upregulated in DRG after CHS. Contact hypersensitivity (CHS) mouse model; CXCR3 antagonist treatment; intradermal CXCL10 injection; behavioral itch and pain assays; DRG neuron calcium imaging/activation Pain Medium 25932692
2015 CXCR3 controls CXCR3-ligand-mediated biased signaling through ligand-specific differential activation of signaling cascades: CXCL11, with higher binding affinity to CXCR3, drives T regulatory 1 (Tr1) cell lineage development, whereas CXCL9 and CXCL10 induce effector Th1/Th17 cells. CXCL11 induces ligand bias at CXCR3 and receptor-biased signaling via atypical chemokine receptor 3 (ACKR3/CXCR7). In vitro T cell differentiation assays; CXCR3 signaling pathway analyses distinguishing CXCL9/CXCL10 vs CXCL11 cascades; transgenic and knockout mouse models of autoimmune disease Journal of leukocyte biology Medium 26657511
2009 CXCL9-CXCR3 constitutes an antifibrotic pathway in the liver: CXCL9 directly suppresses collagen production in human hepatic stellate cells (LX-2) in vitro; CXCR3-/- mice develop increased liver fibrosis associated with decreased intrahepatic IFN-γ+ T cells and reduced IFN-γ mRNA, indicating CXCL9-CXCR3 regulates Th1-associated antifibrotic immune pathways. CXCR3-/- knockout mice; hepatic fibrosis induction; in vitro collagen production assay in LX-2 stellate cells with CXCL9 stimulation; intrahepatic immune cell subset analysis; IFN-γ mRNA measurement Gastroenterology Medium 19344719
2023 A1 astrocyte-secreted CXCL10 induces neuronal ferroptosis via CXCR3: CXCL10 binding to neuronal CXCR3 enhances STAT3 phosphorylation and suppresses SLC7A11 expression, leading to GPX4-dependent lipid peroxidation and ferroptosis in epileptic neurons. Inhibition of ferroptosis blocks A1 astrocyte-induced neurotoxicity. Epilepsy mouse model; ferroptosis inhibitors; CXCL10/CXCR3 pathway analysis; STAT3 phosphorylation assays; SLC7A11 and GPX4 expression measurement; co-culture of astrocytes and neurons; clinical epilepsy tissue analysis Free radical biology & medicine Medium 36610561
2008 Calcineurin inhibitors (CNIs) selectively downregulate CXCR3-B but not CXCR3-A in renal cancer cells; this downregulation of the growth-inhibitory isoform increases cancer cell proliferation and migration via Gi protein-coupled signaling, likely through CXCR3-A, and promotes tumor growth in vivo. CXCR3 splice variant expression analysis; CNI treatment of renal cancer cell lines; proliferation and migration assays; Gi protein inhibition; in vivo tumor growth in xenograft model Journal of the American Society of Nephrology Medium 18832436
2021 NK cell immunosuppressive function requires CXCR3-dependent redistribution to T cell-rich zones of the spleen: type I IFN promotes CXCR3 ligand expression in T cell areas, driving NK cell migration via CXCR3 to enable perforin-dependent elimination of activated CD4+ T cells. CXCR3-deficient NK cells fail to relocate and suppress T cells during LCMV infection. CXCR3-/- mice; LCMV infection model; NK cell trafficking/localization by histology and flow cytometry; exogenous IFN treatment rescue; adenoviral vector immunization model The Journal of clinical investigation High 34314390

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 1199 29207310
2011 CXCR3 in T cell function. Experimental cell research 802 21376175
2011 CXCR3 ligands: redundant, collaborative and antagonistic functions. Immunology and cell biology 785 21221121
2009 CXCR3, inflammation, and autoimmune diseases. Annals of the New York Academy of Sciences 274 19758167
2014 CXCR3 ligands in disease and therapy. Cytokine & growth factor reviews 239 25498524
2010 Review: The chemokine receptor CXCR3 and its ligands CXCL9, CXCL10 and CXCL11 in neuroimmunity--a tale of conflict and conundrum. Neuropathology and applied neurobiology 237 20487305
2020 CXCR3 Ligands in Cancer and Autoimmunity, Chemoattraction of Effector T Cells, and Beyond. Frontiers in immunology 227 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 197 11786428
2020 TGFβ suppresses CD8+ T cell expression of CXCR3 and tumor trafficking. Nature communications 191 32273499
1998 Binding and functional properties of recombinant and endogenous CXCR3 chemokine receptors. The Journal of biological chemistry 167 9660793
2018 CXCL9, CXCL10, CXCL11, and their receptor (CXCR3) in neuroinflammation and neurodegeneration. Advances in clinical and experimental medicine : official organ Wroclaw Medical University 166 29893515
2012 Chemokine receptor trio: CXCR3, CXCR4 and CXCR7 crosstalk via CXCL11 and CXCL12. Cytokine & growth factor reviews 165 22989616
2009 Antifibrotic effects of CXCL9 and its receptor CXCR3 in livers of mice and humans. Gastroenterology 143 19344719
2018 The Role of CXCR3 and Its Chemokine Ligands in Skin Disease and Cancer. Frontiers in medicine 140 30320116
2013 CXCR3, a double-edged sword in tumor progression and angiogenesis. Biochimica et biophysica acta 134 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
2012 Altered CXCR3 isoform expression regulates prostate cancer cell migration and invasion. Molecular cancer 114 22236567
2015 The CXCR3-CXCL11 signaling axis mediates macrophage recruitment and dissemination of mycobacterial infection. Disease models & mechanisms 112 25573892
2014 CXCR3, CXCL10 and type 1 diabetes. Cytokine & growth factor reviews 103 24529741
2009 The chemokine receptors CXCR4 and CXCR3 in cancer. Current oncology reports 93 19216844
2007 CXCR3 axis: role in inflammatory bowel disease and its therapeutic implication. Endocrine, metabolic & immune disorders drug targets 92 17584151
2000 IL-4 enhances keratinocyte expression of CXCR3 agonistic chemokines. Journal of immunology (Baltimore, Md. : 1950) 89 10903743
2009 Antagonism of chemokine receptor CXCR3 inhibits osteosarcoma metastasis to lungs. International journal of cancer 88 19544560
2007 Chemokine receptor CXCR3 mediates T cell recruitment and tissue injury in nephrotoxic nephritis in mice. Journal of the American Society of Nephrology : JASN 88 17538187
2019 CXCR3 regulates CD4+ T cell cardiotropism in pressure overload-induced cardiac dysfunction. JCI insight 85 30779709
2019 The Distinct Roles of CXCR3 Variants and Their Ligands in the Tumor Microenvironment. Cells 85 31216755
2005 CXCR3-binding chemokines: novel multifunctional therapeutic targets. Current drug targets. Immune, endocrine and metabolic disorders 85 15777209
2002 Functional expression of CXCR3 in cultured mouse and human astrocytes and microglia. Neuroscience 85 12074892
2022 The role of CXCR3 and its ligands in cancer. Frontiers in oncology 84 36479091
2011 Expression and agonist responsiveness of CXCR3 variants in human T lymphocytes. Immunology 80 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
2020 Pulmonary Mycobacterium tuberculosis control associates with CXCR3- and CCR6-expressing antigen-specific Th1 and Th17 cell recruitment. JCI insight 76 32554933
2017 Pro-Inflammatory CXCR3 Impairs Mitochondrial Function in Experimental Non-Alcoholic Steatohepatitis. Theranostics 76 29158819
2015 CXCR3 blockade protects against Listeria monocytogenes infection-induced fetal wastage. The Journal of clinical investigation 76 25751061
2005 Overexpression of IFN-induced protein 10 and its receptor CXCR3 in myasthenia gravis. Journal of immunology (Baltimore, Md. : 1950) 76 15843529
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
2001 CXCR3 expression in human central nervous system diseases. Neuropathology and applied neurobiology 69 11437993
2023 Neurotoxic A1 astrocytes promote neuronal ferroptosis via CXCL10/CXCR3 axis in epilepsy. Free radical biology & medicine 68 36610561
2015 CXCR3 chemokine receptor signaling mediates itch in experimental allergic contact dermatitis. Pain 68 25932692
2008 Towards small-molecule CXCR3 ligands with clinical potential. ChemMedChem 68 18442035
2015 CXCR3 in carcinoma progression. Histology and histopathology 67 25663474
2010 Chemokine receptor CXCR3 promotes growth of glioma. Carcinogenesis 66 21051441
2020 CXCL10/CXCR3 Signaling in the DRG Exacerbates Neuropathic Pain in Mice. Neuroscience bulletin 60 33196963
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
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
2007 Targeting of Th1-associated chemokine receptors CXCR3 and CCR5 as therapeutic strategy for inflammatory diseases. Mini reviews in medicinal chemistry 54 18045212
2019 CXCR3-CXCL9: It's All in the Tumor. Immunity 53 31216458
2014 The role of CXCR3 in DSS-induced colitis. PloS one 53 24992040
2015 Small Molecule CXCR3 Antagonists. Journal of medicinal chemistry 52 26535614
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
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 48 37699392
2004 CXCR3-binding chemokines in multiple myeloma. Cancer letters 48 15072832
2022 Location bias contributes to functionally selective responses of biased CXCR3 agonists. Nature communications 46 36195635
2006 CXCR3 and its ligands in a murine model of obliterative bronchiolitis: regulation and function. Journal of immunology (Baltimore, Md. : 1950) 46 16709871
2019 The Role of CXCR3 in Neurological Diseases. Current neuropharmacology 44 29119926
2003 Roles of CCR2 and CXCR3 in the T cell-mediated response occurring during lupus flares. Arthritis and rheumatism 43 14673999
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
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
2016 Increased CXCR3 Expression of Infiltrating Plasma Cells in Hunner Type Interstitial Cystitis. Scientific reports 38 27339056
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
2014 The association of CXCR3 and renal cell carcinoma metastasis. The Journal of urology 37 24518777
2004 Expression of DARC, CXCR3 and CCR5 in giant cell arteritis. Rheumatology (Oxford, England) 37 15572394
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
2011 CXCR3 enhances a T-cell-dependent epidermal proliferative response and promotes skin tumorigenesis. Cancer research 33 21734014
2021 Dual role for CXCR3 and CCR5 in asthmatic type 1 inflammation. The Journal of allergy and clinical immunology 32 34146578
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
2019 Cxcr3-expressing leukocytes are necessary for neurofibroma formation in mice. JCI insight 31 30728335
2022 Evolution, Expression and Functional Analysis of CXCR3 in Neuronal and Cardiovascular Diseases: A Narrative Review. Frontiers in cell and developmental biology 30 35794867
2009 Expression of chemokine receptor CXCR3 by lymphocytes and plasmacytoid dendritic cells in human psoriatic lesions. Archives of dermatological research 30 19517126
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
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
2013 CXCR3 deficiency prolongs Th1-type contact hypersensitivity. Journal of immunology (Baltimore, Md. : 1950) 27 23656737
2023 Phosphorylation barcodes direct biased chemokine signaling at CXCR3. Cell chemical biology 26 37030291
2020 The Role of Chemokine Receptor CXCR3 and Its Ligands in Renal Cell Carcinoma. International journal of molecular sciences 26 33202536
2017 HPV16E7-Induced Hyperplasia Promotes CXCL9/10 Expression and Induces CXCR3+ T-Cell Migration to Skin. The Journal of investigative dermatology 26 29277541
2024 CXCR3-Expressing T Cells in Infections and Autoimmunity. Frontiers in bioscience (Landmark edition) 25 39206903
2022 Biased agonists of the chemokine receptor CXCR3 differentially signal through Gαi:β-arrestin complexes. Science signaling 24 35316095
2006 CXCR3 and IFN protein-10 in Pneumocystis pneumonia. Journal of immunology (Baltimore, Md. : 1950) 24 16849496
2023 The duality of CXCR3 in glioblastoma: unveiling autocrine and paracrine mechanisms for novel therapeutic approaches. Cell death & disease 23 38104126

Missed literature

Know a paper Affinage missed for CXCR3? Flag it for the maintainers and the community.

No submissions yet.