Affinage

CXCL10

C-X-C motif chemokine 10 · UniProt P02778

Length
98 aa
Mass
10.9 kDa
Annotated
2026-06-09
100 papers in source corpus 31 papers cited in narrative 31 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

CXCL10 (IP-10) is a CXC chemokine that orchestrates the recruitment and activation of immune cells, signaling principally through its shared receptor CXCR3 to drive activated T cell chemotaxis and reciprocal cross-desensitization with the related ligand CXCL9/Mig (PMID:9060447, PMID:10589690). Structural and mutational studies define how the ligand engages its receptor: a hydrophobic cleft formed by the N-loop and 40s-loop contacts the CXCR3 N-terminus, while the N-terminal Arg-8 is critical for signaling and a partially overlapping but distinct surface centered on Arg-22 mediates heparin/GAG binding that is dispensable for CXCR3 engagement (PMID:12173928, PMID:12571234); the protein can also assemble into a novel N-terminally-linked tetramer presenting heparin-binding sites at the dimer interfaces (PMID:18560148). Through CXCR3 CXCL10 elevates intracellular Ca2+ and activates p38/ERK MAPK signaling, outputs that underlie diverse cellular consequences including synovial fibroblast invasion and MMP-1 induction in arthritis (PMID:21811993), increased neuronal excitability and neuropathic pain (PMID:33196963), anti-angiogenic suppression of endothelial migration via cAMP/PKA and the VEGF/MMP-13 axis (PMID:22815829, PMID:28623423), and accumulation of T cells and parasites in the CNS during infection (PMID:19827943). Beyond CXCR3, CXCL10 acts through TLR4 in pancreatic beta cells to switch Akt/JNK signaling toward apoptosis and impair insulin secretion (PMID:19187771), and engages both CXCR3 and TLR4 in alveolar macrophages to induce CCL12 and promote premetastatic niche formation (PMID:35398531). CXCL10 transcription is induced by IFN-γ, NF-κB, IRF3, NFAT, PKC, and stress-responsive PERK signaling (PMID:25342131, PMID:9705166, PMID:28855240, PMID:28233092, PMID:28065589) and repressed epigenetically by EZH2/G9a-mediated H3K27me3/H3K9me3 at its promoter (PMID:29053336, PMID:32238853). The mature chemokine is post-translationally inactivated by DPP4-mediated N-terminal truncation, which generates a CXCR3-binding but non-signaling antagonist (PMID:30026741), and by the Leishmania protease GP63, which cleaves after Ala-81 to abolish chemotactic activity (PMID:31440475).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1997 High

    Established CXCL10's target-cell selectivity and receptor sharing, answering which leukocytes it recruits and through what receptor.

    Evidence Recombinant IP-10 chemotaxis and cross-desensitization assays with CXCL9 in vitro and in vivo

    PMID:9060447

    Open questions at the time
    • Did not define the structural basis of CXCR3 engagement
    • Anti-tumor and anti-angiogenic activities noted but not mechanistically dissected
  2. 1999 Medium

    Confirmed CXCR3-dependent functional signaling in non-leukocyte cells, extending CXCL10's action to resident tissue cells.

    Evidence Ca2+ flux and proliferation assays in CXCR3-expressing mesangial cells with recombinant IP-10

    PMID:10589690

    Open questions at the time
    • Proliferative effect on mesangial cells not linked to downstream effectors
    • In vivo relevance to glomerulonephritis not directly tested
  3. 2002 High

    Defined the receptor-interaction surface of CXCL10, answering how the chemokine fold engages the CXCR3 N-terminus.

    Evidence NMR structure with CXCR3 N-terminal peptide titration

    PMID:12173928

    Open questions at the time
    • No structure of the full ligand-receptor complex
    • Functional contribution of individual contact residues not tested in this study
  4. 2003 High

    Separated the CXCR3-signaling and heparin/GAG-binding determinants, resolving whether GAG binding is needed for receptor activation.

    Evidence Alanine-scanning mutagenesis with binding, chemotaxis, Ca2+, internalization assays and GAG-deficient CHO cells

    PMID:12571234

    Open questions at the time
    • Performed on murine CXCL10; human residue equivalences inferred
    • Role of GAG binding in vivo for haptotactic gradients not addressed
  5. 2008 High

    Revealed a distinct oligomerization mode, addressing how CXCL10 may present multiple GAG-binding sites.

    Evidence X-ray crystallography of mouse IP-10

    PMID:18560148

    Open questions at the time
    • Functional significance of the tetramer for signaling not established
    • Tetramer differs from human IP-10 forms; species relevance unclear
  6. 2009 Medium

    Identified a CXCR3-independent receptor (TLR4) and a pro-apoptotic signaling mode in beta cells, expanding CXCL10's receptor repertoire.

    Evidence Recombinant CXCL10 on human islets with CXCR3 blockade and Akt/JNK/PAK-2 western blots

    PMID:19187771

    Open questions at the time
    • TLR4 not confirmed as a direct binding partner by binding assay
    • How CXCL10 engages TLR4 structurally is unknown
  7. 2009 Medium

    Defined CXCL10/CXCR3 as required for CNS T cell and parasite accumulation during infection, separating recruitment from systemic parasitemia.

    Evidence CXCL10-/- and CXCR3-/- mouse trypanosomiasis infection models

    PMID:19827943

    Open questions at the time
    • Cellular source of brain CXCL10 not pinpointed
    • Single infection paradigm
  8. 2009 Medium

    Established constitutive neuronal storage and developmental expression, distinguishing inducible from constitutive CXCL10 pools.

    Evidence Immunohistochemistry, electron microscopy of dense-core vesicles, ELISA, developmental expression analysis

    PMID:19919575

    Open questions at the time
    • Functional consequence of neuronal CXCL10 release not directly tested
    • Mechanism of constitutive secretion not defined
  9. 2012 Medium

    Mapped the anti-angiogenic mechanism to a C-terminal fragment acting via cAMP/PKA and calpain inhibition, defining a functional domain.

    Evidence Endothelial motility/tube formation and in vivo Matrigel assays with the IP-10p peptide and CXCR3 neutralization

    PMID:22815829

    Open questions at the time
    • Whether the C-terminal fragment is generated physiologically not shown
    • Relationship to GAG-binding C-terminal residues unaddressed
  10. 2017 Medium

    Placed CXCL10 upstream of VEGF/MMP-13 suppression in vivo, ordering the anti-angiogenic pathway hierarchy.

    Evidence AAV9-driven CXCL10 overexpression, CXCL10/CXCR3 neutralization, MMP-13 inhibition in mouse cornea

    PMID:28623423

    Open questions at the time
    • Direct molecular link from CXCR3 to VEGF/MMP-13 transcription not resolved
    • Single tissue model
  11. 2017 Low

    Demonstrated context-dependent pro-tumor signaling (EMT/metastasis via MMP-2), contrasting with the anti-angiogenic role.

    Evidence shRNA, overexpression, Transwell, xenograft, microarray in hepatocellular carcinoma cells

    PMID:28670372

    Open questions at the time
    • CXCL10→MMP-2 connection identified only by microarray, not mechanistically validated
    • Receptor mediating the EMT effect not defined
  12. 2018 Medium

    Showed enzymatic generation of a CXCR3-binding non-signaling antagonist by DPP4, establishing a post-translational off-switch.

    Evidence Digital ELISA for agonist/antagonist forms, DPP4 activity assay, immunohistochemistry in TB lesions

    PMID:30026741

    Open questions at the time
    • Antagonist potency at CXCR3 not quantified here
    • Causal role of antagonist in TB outcome correlative
  13. 2019 High

    Identified a pathogen protease (GP63) cleavage site at Ala-81 that inactivates chemotaxis, defining an immune-evasion mechanism.

    Evidence In vitro protease cleavage with site sequencing and T cell chemotaxis/CXCR3 signaling assays

    PMID:31440475

    Open questions at the time
    • In vivo contribution to Leishmania persistence not demonstrated
    • Whether cleaved fragment retains any receptor binding not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CXCL10 discriminates among CXCR3, TLR4, and proteolytic regulation to produce opposing pro- versus anti-tumor and pro- versus anti-angiogenic outcomes in different tissues remains unresolved.
  • No structure of CXCL10 bound to TLR4 or full-length CXCR3
  • Determinants of context-dependent functional switching not defined
  • Physiological generators of the anti-angiogenic C-terminal fragment unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 4 GO:0008289 lipid binding 2
Localization
GO:0005576 extracellular region 3 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-74160 Gene expression (Transcription) 5 R-HSA-162582 Signal Transduction 4 R-HSA-168256 Immune System 4
Partners
CXCR3DPP4TLR4

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 The NMR structure of IP-10/CXCL10 was solved, revealing an unusual structural feature that may explain its ability to bind both CXCR3 and CCR3. The surface of IP-10 that interacts with the N-terminus of CXCR3 was defined and involves a hydrophobic cleft formed by the N-loop and 40s-loop region, similar to IL-8; an additional interaction region was identified at the N-terminus and 30s-loop of IP-10. NMR spectroscopy with CXCR3 N-terminal peptide titration Biochemistry High 12173928
2003 Mutational analysis of murine IP-10/CXCL10 identified distinct but partially overlapping CXCR3 and heparin (GAG) binding sites. Arg-22 had the largest effect on heparin binding; residues Arg-20, Ile-24, Lys-26, Lys-46, and Lys-47 also contributed. Arg-8 (N-terminal, preceding first cysteine) was critical for CXCR3 signaling. GAG-deficient CHO cells showed that heparin/GAG binding is not required for CXCR3 binding and signaling. Extensive alanine-exchange mutagenesis with heparin binding, CXCR3 binding, chemotaxis, Ca2+ flux, and CXCR3 internalization assays; GAG-deficient CHO cell experiments The Journal of biological chemistry High 12571234
2008 Crystal structure of mouse IP-10/CXCL10 revealed a novel tetrameric association in which two conventional CXC chemokine dimers associate through their N-terminal regions to form a 12-stranded elongated beta-sheet. This tetramer differs from previously described tetramers of human IP-10, platelet factor 4, and NAP-2. Two heparin-binding sites were identified at the interface of each of the two beta-sheet dimers. X-ray crystallography Acta crystallographica. Section D, Biological crystallography High 18560148
1997 Recombinant human IP-10 (rIP-10) has no chemotactic activity on neutrophils but specifically targets lymphocytes, acting as a chemotactic factor for stimulated (but not resting) T cells. rIP-10 and rHuMig show reciprocal desensitization on activated T cells and share the receptor CXCR3. rIP-10 also inhibits neovascularization, inhibits hematopoietic progenitor cells, and exerts anti-tumor effects. Recombinant protein chemotaxis assays in vitro and in vivo; receptor desensitization assays Journal of leukocyte biology High 9060447
2009 CXCL10 impairs beta cell viability and function through TLR4 signaling rather than CXCR3. CXCL10 treatment of human islets decreased beta cell viability, impaired insulin secretion, and decreased insulin mRNA. Mechanistically, CXCL10 induced sustained activation of Akt and JNK and cleavage of PAK-2, switching Akt signals from proliferation to apoptosis. CXCR3 blockade did not abolish these effects, implicating TLR4 as a binding partner/receptor for CXCL10 in beta cells. Recombinant CXCL10 treatment of human islets; CXCR3 blockade experiments; western blotting for Akt, JNK, PAK-2 signaling Cell metabolism Medium 19187771
2011 CXCL10/CXCR3 signaling regulates synovial fibroblast (FLS) invasion in rheumatoid arthritis via an autocrine/paracrine mechanism. CXCL10 treatment increased FLS invasiveness 2-fold; anti-CXCR3 antibody and CXCR3 inhibitor AMG487 reduced invasiveness up to 77% in DA rat FLS and 58% in RA FLS. CXCR3 blockade reduced MMP-1 levels by 65%, inhibited intracellular calcium influx, and interfered with actin cytoskeleton reorganization and lamellipodia formation. Matrigel invasion assay, anti-CXCR3 antibody and pharmacological inhibitor treatment, MMP-1 ELISA, intracellular calcium measurement, actin cytoskeleton imaging Arthritis and rheumatism Medium 21811993
2012 CXCL10 inhibits angiogenesis through CXCR3-dependent mechanisms involving cAMP production and PKA activation (inhibiting cell migration) and inhibition of VEGF-mediated m-calpain activation. A 21-amino-acid C-terminal alpha-helical fragment of IP-10 (residues 77-98, IP-10p) recapitulates these anti-angiogenic effects, inhibiting VEGF-induced endothelial motility and tube formation in vitro and vessel formation in vivo; CXCR3 neutralizing antibody blocked IP-10p effects. In vitro endothelial motility and tube formation assays; in vivo Matrigel plug assay; CXCR3 neutralizing antibody blockade; cAMP measurement; PKA activity assay; calpain activity assay PloS one Medium 22815829
2015 CXCL10 triggers early microglial activation following oligodendrocyte apoptosis in the cuprizone model. CXCL10-deficient mice showed significantly reduced early microglial activation and ameliorated cuprizone toxicity. In vitro, recombinant CXCL10 induced migration and a pro-inflammatory phenotype in cultured microglia without affecting phagocytic activity or proliferation. In situ hybridization showed Cxcl10 mRNA is mainly expressed by astrocytes (and some oligodendrocytes) under these conditions. CXCL10-deficient knockout mice; in vitro recombinant CXCL10 treatment of microglia; genome-wide gene expression; in situ hybridization Journal of immunology Medium 25725102
2017 CXCL10 suppresses hem- and lymph-angiogenesis in inflamed corneas through suppression of angiogenic factors including VEGFa, VEGFc, and MMP-13 in vivo. AAV9-driven epithelial CXCL10 expression suppressed infection- and inflammation-induced angiogenesis; CXCL10 or CXCR3 neutralization promoted angiogenesis. Inhibition of MMP-13 (but not TIMPs) attenuated neovascularization, placing MMP-13 downstream of angiogenic signals but not upstream of CXCL10. AAV9 vector-driven CXCL10 overexpression; CXCL10 and CXCR3 neutralizing antibodies; MMP-13 inhibitors; in vivo mouse corneal model Angiogenesis Medium 28623423
2018 EZH2 and G9a cooperatively repress CXCL10 expression in idiopathic pulmonary fibrosis fibroblasts through histone H3K27 trimethylation and H3K9 methylation at the CXCL10 promoter. EZH2 and G9a physically interact; knockdown of either reduces the other's histone mark and restores CXCL10 expression. TGF-β1 induces this epigenetic repression. Re-ChIP and proximity ligation assays confirmed co-occupancy of EZH2 and G9a at the CXCL10 promoter. Chromatin immunoprecipitation (ChIP), Re-ChIP, proximity ligation assay, siRNA knockdown, pharmacological inhibition, promoter analysis American journal of respiratory cell and molecular biology High 29053336
2017 IP-10/CXCL10 gene induction in pancreatic beta cells is regulated by NFAT signaling via calcineurin-dependent pathways in response to oxidative or inflammatory stress. Sustained NFAT and p300 histone acetyltransferase association with the IP-10 gene promoter requires p38 and JNK MAPK activity, which differentially regulate IP-10 expression and protein release. Transgenic mouse studies, in vitro signaling pathway analysis, NFAT/p300 ChIP, MAPK inhibition Diabetes Medium 28855240
2019 Leishmania major virulence factor GP63 (glycoprotein-63) cleaves CXCL10 after amino acid A81 at the base of its C-terminal alpha-helix, inactivating its chemotactic function. This cleavage is specific to CXCR3-binding chemokines (CXCL10 and homologs) but not to distantly related chemokines (CXCL8, CCL22). The cleaved CXCL10 cannot signal through CXCR3 and fails to support T cell chemotaxis in vitro. In vitro protease cleavage assay, site identification by sequencing, T cell chemotaxis assay, CXCR3 signaling assay Frontiers in cellular and infection microbiology High 31440475
2018 DPP4 (CD26) can N-terminally truncate CXCL10 to generate an antagonist form capable of binding CXCR3 but unable to induce signaling. In tuberculosis lesions, higher levels of antagonist CXCL10 and reduced DPP4 enzyme activity were found in plasma of TB patients; DPP4-positive T cells were associated with CXCL10-secreting multinucleated giant cells, suggesting membrane-bound DPP4 can inactivate secreted CXCL10 locally. Simoa digital ELISA for agonist/antagonist CXCL10, DPP4 enzyme activity assay, immunohistochemistry, confocal microscopy Frontiers in immunology Medium 30026741
2014 MRP8/MRP14 (S100A8/A9), an endogenous DAMP, induces IP-10/CXCL10 expression in monocytes/macrophages via TLR4 and TRIF (not MyD88). Full IP-10 induction requires synergistic activation of NF-κB and IRF3 transcription factors. MRP8/MRP14-induced chemotaxis of CXCR3+ cells was dependent on IP-10 production. THP-1 cell stimulation, TLR4/MyD88/TRIF pathway dissection, NF-κB and IRF3 reporter/western blot, neutralizing antibody, in vivo mouse trauma/hemorrhagic shock model FASEB journal Medium 25342131
2007 In human keratinocytes, IFN-γ induces IP-10 mRNA accumulation in a time- and dose-dependent manner. Superexpression occurs with IFN-γ combined with TNF-α or IL-1. Nuclear run-on experiments showed constitutively high IP-10 gene transcription in unstimulated keratinocytes not further increased by IFN-γ/TNF-α, indicating post-transcriptional regulation. PKC inhibitor H7 decreased IP-10 mRNA accumulation, implicating PKC in IP-10 expression regulation. RT-PCR, Northern blot, nuclear run-on transcription assay, HPLC protein isolation, ELISA, PKC inhibitor treatment Archives of dermatological research Medium 9705166
1999 IP-10 (CXCL10) and Mig (CXCL9) sharing of receptor CXCR3 was confirmed in glomerulonephritis; IP-10 induced intracellular Ca2+ influx in mesangial cells expressing CXCR3 and directly induced mesangial cell proliferation. Flow cytometry (CXCR3 expression), intracellular Ca2+ flux measurement, cell proliferation assay with recombinant IP-10 Journal of the American Society of Nephrology Medium 10589690
2020 CXCL10/CXCR3 signaling in dorsal root ganglion (DRG) neurons increases neuronal excitability and contributes to neuropathic pain. CXCL10 increased the number of action potentials in DRG neurons via CXCR3 (not increased in Cxcr3-/- neurons). CXCL10 activated p38 and ERK in DRG neurons; p38 inhibitor SB203580 decreased CXCL10-induced APs. Intra-DRG Cxcr3 shRNA attenuated spinal nerve ligation-induced mechanical allodynia and heat hyperalgesia. Electrophysiology (action potential recording), Cxcr3 knockout mice, shRNA knockdown, p38/ERK western blot, pharmacological inhibition Neuroscience bulletin Medium 33196963
2009 Infected CXCL10-/- or CXCR3-/- mice demonstrated reduced accumulation of trypanosomes and T cells in the brain parenchyma during experimental African trypanosomiasis, while parasitemia levels were similar to wild-type, establishing that IFN-γ-dependent CXCL10/CXCR3 signaling is critical for brain parenchymal T cell and parasite accumulation specifically. CXCL10-/- and CXCR3-/- knockout mouse infection model, tissue cell quantification, parasitemia measurement, CXCL10 ELISA The Journal of infectious diseases Medium 19827943
2017 CXCL10 accelerates epithelial-mesenchymal transition (EMT) and metastasis of hepatocellular carcinoma cells via activation of MMP-2 expression. CXCL10 overexpression enhanced migration, invasion, and metastasis in vitro and in vivo; CXCL10 silencing inhibited these. Microarray analysis identified MMP-2 as a downstream factor of CXCL10. shRNA knockdown, overexpression, Transwell migration/invasion assay, in vivo xenograft, microarray gene expression analysis American journal of translational research Low 28670372
2019 Viperin regulates chondrogenic differentiation via CXCL10 secretion, which in turn modulates TGF-β/SMAD2/3 signaling activity in chondrocytes. Disturbances in this viperin-CXCL10-TGF-β/SMAD2/3 axis were observed in cartilage-hair hypoplasia (CHH) chondrocytic cells. siRNA knockdown, overexpression, ELISA, label-free MS proteomics, promoter reporter assays, immunoblotting The Journal of biological chemistry Medium 30718282
2017 JAK2V617F mutation drives cell-autonomous CXCL10 expression through NF-κB signaling. Pharmacological inhibition of mutated JAK2 kinase inhibits CXCL10 expression. NFκB is activated downstream of JAK2V617F and directly induces CXCL10 transcription, as demonstrated by luciferase reporter assays and ChIP. Cytokine array, qPCR, JAK inhibitor treatment, NF-κB luciferase reporter, ChIP, western blotting, immunofluorescence; Ba/F3 cells lacking CXCL10 receptor to exclude autocrine signaling Journal of cancer research and clinical oncology Medium 28233092
2017 PERK pathway positively regulates CXCL10 expression under ER stress conditions, while XBP1 (activated by IRE1α) negatively regulates it. PERK knockdown attenuated ER stress-induced CXCL10 mRNA expression associated with decreased NF-κB RelA and STAT3 phosphorylation; XBP1 knockdown enhanced CXCL10 expression with increased NF-κB RelA and STAT3 phosphorylation. Blockade of NF-κB or STAT3 markedly diminished CXCL10 expression. siRNA knockdown of PERK and XBP1, NF-κB and STAT3 pharmacological inhibition, RT-PCR, ELISA, western blot Experimental eye research Medium 28065589
2022 CXCL10 induces CCL12 expression in alveolar macrophages (AMs) by activating both CXCR3 and TLR4, promoting premetastatic niche formation. CXCR3/TLR4 deficiency or inhibition reduces CCL12 expression and subsequent monocytic MDSC recruitment. Ube2o is a negative modulator of CXCL10-induced CCL12 expression; its downregulation under tumor conditions enhances TAK1-NF-κB/ERK/JNK signaling and CXCL10-induced CCL12 expression by promoting TRAF6 polyubiquitination and inhibiting DDX3X degradation. CXCR3/TLR4 knockout mice, siRNA, pharmacological inhibition, western blot for signaling intermediates, in vivo lung metastasis model Cancer letters Medium 35398531
2020 Human chorionic gonadotropin (hCG) inhibits CXCL10 expression in decidual stromal cells by inducing H3K27me3 histone methylation at Region 4 of the CXCL10 promoter, mediated through EZH2 (a member of the PRC2 complex). This regulation has functional consequences for CD8 cell recruitment to the maternal-fetal interface. Chromatin immunoprecipitation, in vitro decidual cell models, siRNA for EZH2, hCG treatment, CD8 cell recruitment assay Scientific reports Medium 32238853
1999 Recombinant vaccinia viruses encoding CRG-2 (murine IP-10/CXCL10 homolog) conferred antiviral activity in vivo in athymic nude mice. Virus-encoded CRG-2 enhanced NK cell cytolytic activity 2- to 3-fold and increased splenic cellularity, with increased mononuclear cell infiltration in the liver. Control of viral replication required NK cells and type I IFNs (IFN-α, IFN-β) as established by neutralizing/depleting antibody experiments. Recombinant vaccinia virus expression system, in vivo infection model, NK cell depletion, IFN neutralizing antibodies Journal of virology Medium 9882354
2009 CXCL10 is constitutively expressed and stored in large dense-core vesicles in neurons, released constitutively at low levels. Neuronal CXCL10 expression is not regulated by injury or stress. In vivo CXCL10 peak expression during brain development correlates with the presence of CXCR3-expressing CD11b+ and GFAP+ glial cells, suggesting a role in glial recruitment/homing during embryogenesis. Immunohistochemistry, electron microscopy (vesicle localization), ELISA for secretion, in vivo developmental expression analysis Journal of neurochemistry Medium 19919575
2022 MEK inhibitor combined with PEM/CDDP chemotherapy triggers CXCL10 secretion by cancer cells through OPTN-dependent mitophagy in a mitochondrial DNA- and TLR9-dependent manner. TLR9 or autophagy/mitophagy inhibition abolished CXCL10 production and the anti-tumor efficacy of the combination therapy. This places TLR9 and mitophagy upstream of CXCL10 induction in this context. In vitro cancer cell treatment, genetic inhibition of TLR9 and autophagy/mitophagy genes, in vivo lung tumor models, OPTN knockout Cancer cell Medium 35051357
2023 MLKL (mixed-lineage kinase domain-like protein) promotes CXCL10 secretion from pancreatic acinar cells, which in turn drives M1 macrophage polarization. Mlkl knockout mice showed reduced CXCL10 secretion and reduced M1 polarization during experimental pancreatitis. In vitro CXCL10 neutralization impaired the pro-M1 effect of conditioned medium from cerulein-treated acinar cells; in vivo CXCL10 neutralization reduced M1 polarization and AP severity. This effect was independent of RIPK3. Mlkl-/- and Ripk3-/- mice, in vitro neutralizing antibody, in vivo neutralizing antibody, conditioned medium experiments, flow cytometry for macrophage subtypes Cell death & disease Medium 36828808
2007 Palmitic acid (saturated FFA) induces CXCL10/IP-10 gene expression in human macrophages via NF-κB activation. Two structurally distinct NF-κB inhibitors blocked PA-induced IP-10 gene expression. Conditioned medium from PA-treated cells increased lymphocyte migration by 41%, which was significantly reduced by IP-10-neutralizing antibody. Gene expression analysis, NF-κB activity assay, pharmacological NF-κB inhibition, IP-10 neutralizing antibody, lymphocyte migration assay Biochemical and biophysical research communications Low 17467667
2018 S. aureus downregulates IP-10/CXCL10 production in monocytes through activation of MAPKs p38 and ERK and inhibition of STAT1 signaling, reducing Th1 cell-recruiting chemokine production. This suppression is independent of peptidoglycan-induced IL-10. The net effect is inhibition of superantigen-induced Th1 cell recruitment. Monocyte stimulation assays, MAPK/STAT1 western blot, pharmacological pathway inhibitors, T cell chemotaxis assay Journal of immunology Low 28122962
2018 CXCL10 expression is determined by a subset of plasmacytoid dendritic cells (pDCs) following TLR7 stimulation. CXCL10 expression in dendritic cells requires IFNAR (type I IFN receptor) signaling; IFNAR blocking and deficiency abolished CXCR3 ligand expression in Flt3L-derived DCs. CXCL10+ and CXCL10- pDC populations are transcriptionally distinct, defining pDC heterogeneity. Chemokine reporter mouse, TLR7 stimulation, IFNAR blocking/deficiency, single-cell transcriptomics Immunology and cell biology Medium 29870118

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 CXCL10/IP-10 in infectious diseases pathogenesis and potential therapeutic implications. Cytokine & growth factor reviews 657 21802343
1997 Mig and IP-10: CXC chemokines that target lymphocytes. Journal of leukocyte biology 655 9060447
2008 CXCL10 and autoimmune diseases. Autoimmunity reviews 293 19105984
2022 MEK inhibition overcomes chemoimmunotherapy resistance by inducing CXCL10 in cancer cells. Cancer cell 191 35051357
2009 CXCL10 impairs beta cell function and viability in diabetes through TLR4 signaling. Cell metabolism 186 19187771
2018 Chemokines beyond chemo-attraction: CXCL10 and its significant role in cancer and autoimmunity. Cytokine 175 29449068
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
1990 Identification of CRG-2. An interferon-inducible mRNA predicted to encode a murine monokine. The Journal of biological chemistry 163 2118520
2010 Islet inflammation and CXCL10 in recent-onset type 1 diabetes. Clinical and experimental immunology 159 20059481
2021 Immune cell and tumor cell-derived CXCL10 is indicative of immunotherapy response in metastatic melanoma. Journal for immunotherapy of cancer 140 34593622
1996 Genes for chemokines MuMig and Crg-2 are induced in protozoan and viral infections in response to IFN-gamma with patterns of tissue expression that suggest nonredundant roles in vivo. Journal of immunology (Baltimore, Md. : 1950) 120 8906829
2015 CXCL10 triggers early microglial activation in the cuprizone model. Journal of immunology (Baltimore, Md. : 1950) 117 25725102
2014 The multifaceted functions of CXCL10 in cardiovascular disease. BioMed research international 116 24868552
2007 CXCL10/IP-10: a missing link between inflammation and anti-angiogenesis in preeclampsia? The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 114 17943641
2015 Oncogenic CXCL10 signalling drives metastasis development and poor clinical outcome. British journal of cancer 113 26042934
2002 The CXCR3 binding chemokine IP-10/CXCL10: structure and receptor interactions. Biochemistry 113 12173928
2014 CXCR3, CXCL10 and type 1 diabetes. Cytokine & growth factor reviews 103 24529741
1999 Role for interactions between IP-10/Mig and CXCR3 in proliferative glomerulonephritis. Journal of the American Society of Nephrology : JASN 102 10589690
2012 CXCL10: a candidate biomarker in transplantation. Clinica chimica acta; international journal of clinical chemistry 92 22366165
1994 IFN and virus-inducible expression of an immediate early gene, crg-2/IP-10, and a delayed gene, I-A alpha in astrocytes and microglia. Journal of immunology (Baltimore, Md. : 1950) 92 8301141
2012 The interaction between CXCL10 and cytokines in chronic inflammatory arthritis. Autoimmunity reviews 90 23092582
2007 Palmitic acid induces IP-10 expression in human macrophages via NF-kappaB activation. Biochemical and biophysical research communications 88 17467667
2015 CXCL10/IP-10 is a biomarker and mediator for Kawasaki disease. Circulation research 87 25605650
2003 CXCR3 and heparin binding sites of the chemokine IP-10 (CXCL10). The Journal of biological chemistry 87 12571234
1999 The interferon-inducible chemokines MuMig and Crg-2 exhibit antiviral activity In vivo. Journal of virology 86 9882354
2018 IP-10 is highly involved in HIV infection. Cytokine 84 30472104
2015 IP-10/CXCL10 attracts regulatory T cells: Implication for pancreatic cancer. Oncoimmunology 79 26405599
2011 CXCL10 and its receptor CXCR3 regulate synovial fibroblast invasion in rheumatoid arthritis. Arthritis and rheumatism 78 21811993
2012 An IP-10 (CXCL10)-derived peptide inhibits angiogenesis. PloS one 77 22815829
2011 Dysregulated expression of MIG/CXCL9, IP-10/CXCL10 and CXCL16 and their receptors in systemic sclerosis. Arthritis research & therapy 72 21303517
2015 IP-10 differentiates between active and latent tuberculosis irrespective of HIV status and declines during therapy. The Journal of infection 69 25597826
2022 CXCL10 Chemokine: A Critical Player in RNA and DNA Viral Infections. Viruses 68 36366543
2007 Induction of IP-10 (CXCL10) in astrocytes following Japanese encephalitis. Neuroscience letters 68 17287085
2009 Expression and role of CXCL10 during the encephalitic stage of experimental and clinical African trypanosomiasis. The Journal of infectious diseases 65 19827943
2023 KRT17 Promotes T-lymphocyte Infiltration Through the YTHDF2-CXCL10 Axis in Colorectal Cancer. Cancer immunology research 63 37129929
2017 CXCL10/IP-10 Neutralization Can Ameliorate Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome in Rats. PloS one 61 28046003
2020 CXCL10/CXCR3 Signaling in the DRG Exacerbates Neuropathic Pain in Mice. Neuroscience bulletin 60 33196963
2020 Role of Chemokine (C-X-C Motif) Ligand 10 (CXCL10) in Renal Diseases. Mediators of inflammation 55 32089645
2020 CXCL-10: a new candidate for melanoma therapy? Cellular oncology (Dordrecht, Netherlands) 53 32207043
2014 Injury-induced MRP8/MRP14 stimulates IP-10/CXCL10 in monocytes/macrophages. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 52 25342131
1998 Chemokine IP-10 expression in cultured human keratinocytes. Archives of dermatological research 52 9705166
2018 Interplay between EZH2 and G9a Regulates CXCL10 Gene Repression in Idiopathic Pulmonary Fibrosis. American journal of respiratory cell and molecular biology 51 29053336
2023 Spatially resolved transcriptomics reveals pro-inflammatory fibroblast involved in lymphocyte recruitment through CXCL8 and CXCL10. eLife 48 36648332
2015 CXCL10 in psoriasis. Advances in medical sciences 47 26318079
2014 IP-10 in autoimmune thyroiditis. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme 45 24977661
2018 Chemokine CXCL10 and Coronavirus-Induced Neurologic Disease. Viral immunology 43 30109979
2014 Cognitive Status Correlates with CXCL10/IP-10 Levels in Parkinson's Disease. Parkinson's disease 42 25386381
2007 Expression of IP-10 related to angiogenesis in uterine cervical cancers. British journal of cancer 41 17505511
2004 IP-10 and type 1 diabetes: a question of time and location. Autoimmunity 41 15518041
2011 CXCL10 reduces melanoma proliferation and invasiveness in vitro and in vivo. The British journal of dermatology 39 21155750
2022 CXCL10 conditions alveolar macrophages within the premetastatic niche to promote metastasis. Cancer letters 38 35398531
2017 CXCL10 accelerates EMT and metastasis by MMP-2 in hepatocellular carcinoma. American journal of translational research 38 28670372
2017 Pancreatic β-Cell-Derived IP-10/CXCL10 Isletokine Mediates Early Loss of Graft Function in Islet Cell Transplantation. Diabetes 36 28855240
2016 Progranulin inhibits expression and release of chemokines CXCL9 and CXCL10 in a TNFR1 dependent manner. Scientific reports 36 26892362
2023 MLKL signaling regulates macrophage polarization in acute pancreatitis through CXCL10. Cell death & disease 35 36828808
2018 Interplay of DDP4 and IP-10 as a Potential Mechanism for Cell Recruitment to Tuberculosis Lesions. Frontiers in immunology 35 30026741
2017 CXCL10 suppression of hem- and lymph-angiogenesis in inflamed corneas through MMP13. Angiogenesis 35 28623423
2004 Regulation of neuroinflammation: the role of CXCL10 in lymphocyte infiltration during autoimmune encephalomyelitis. Journal of cellular biochemistry 35 15108349
2017 High CXCL10/IP-10 levels are a hallmark in the clinical evolution of the HIV infection. Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases 34 29122683
2005 Significance of serum CXCL10/IP-10 level in type 1 diabetes. Journal of autoimmunity 34 16309891
2021 IP-10 (CXCL10) Can Trigger Emergence of Dormant Breast Cancer Cells in a Metastatic Liver Microenvironment. Frontiers in oncology 33 34123844
2022 Role of CXCL10 in Spinal Cord Injury. International journal of medical sciences 32 36483597
2015 Serum levels of leptin and IP-10 in preeclampsia compared to controls. Archives of gynecology and obstetrics 32 25693758
2023 FABP4 in LSECs promotes CXCL10-mediated macrophage recruitment and M1 polarization during NAFLD progression. Biochimica et biophysica acta. Molecular basis of disease 31 37487374
2019 Pathogen Evasion of Chemokine Response Through Suppression of CXCL10. Frontiers in cellular and infection microbiology 31 31440475
1995 Regulatory mechanisms of MuRantes and CRG-2 chemokine gene induction in central nervous system glial cells by virus. Brain, behavior, and immunity 31 8903850
2019 Accumulate evidence for IP-10 in diagnosing pulmonary tuberculosis. BMC infectious diseases 30 31666025
2023 CXCL10 and Nrf2-upregulated mesenchymal stem cells reinvigorate T lymphocytes for combating glioblastoma. Journal for immunotherapy of cancer 29 38056897
2019 Cell-Free DNA and CXCL10 Derived from Bronchoalveolar Lavage Predict Lung Transplant Survival. Journal of clinical medicine 27 30781765
2017 PERK and XBP1 differentially regulate CXCL10 and CCL2 production. Experimental eye research 27 28065589
2006 Expression of IP-10/CXCL10 is upregulated by double-stranded RNA in BEAS-2B bronchial epithelial cells. Respiration; international review of thoracic diseases 27 16490936
2022 A Teleost CXCL10 Is Both an Immunoregulator and an Antimicrobial. Frontiers in immunology 26 35795684
2022 Chemokine CXCL10 Modulates the Tumor Microenvironment of Fibrosis-Associated Hepatocellular Carcinoma. International journal of molecular sciences 26 35897689
2017 CXCL10 is upregulated in synovium and cartilage following articular fracture. Journal of orthopaedic research : official publication of the Orthopaedic Research Society 26 28906016
2022 Transcriptional expression of CXCL10 and STAT1 in lupus nephritis and the intervention effect of triptolide. Clinical rheumatology 25 36374433
2016 Targeting the IFN-γ/CXCL10 pathway in lichen planus. Medical hypotheses 25 27241258
2016 PDGFR-alpha inhibits melanoma growth via CXCL10/IP-10: a multi-omics approach. Oncotarget 25 27764787
2021 Association of chemokines IP-10/CXCL10 and I-TAC/CXCL11 with insulin resistance and enhance leukocyte endothelial arrest in obesity. Microvascular research 24 34534571
2020 Human Chorionic Gonadotropin modulates CXCL10 Expression through Histone Methylation in human decidua. Scientific reports 24 32238853
2020 CXCL5, CXCL8, and CXCL10 regulation by bacteria and mechanical forces in periodontium. Annals of anatomy = Anatomischer Anzeiger : official organ of the Anatomische Gesellschaft 24 33221386
2024 CXCL9, CXCL10, and CCL19 synergistically recruit T lymphocytes to skin in lichen planus. JCI insight 22 39190494
2017 Staphylococcus aureus Downregulates IP-10 Production and Prevents Th1 Cell Recruitment. Journal of immunology (Baltimore, Md. : 1950) 22 28122962
2019 Urinary CXCL9 and CXCL10 Levels and Acute Renal Graft Rejection. International journal of organ transplantation medicine 20 31285802
2017 COMMD7 promotes hepatocellular carcinoma through regulating CXCL10. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 20 28142122
2021 Impact of Plasma IP-10/CXCL10 and RANTES/CCL5 Levels on Neurocognitive Function in HIV Treatment-Naive Patients. AIDS research and human retroviruses 19 33472520
2013 Differential expression of CXCL1, CXCL9, CXCL10 and CXCL12 chemokines in alopecia areata. Iranian journal of immunology : IJI 19 23502337
2009 Expression of CXCL10 in cultured cortical neurons. Journal of neurochemistry 19 19919575
2024 The interplay of Cxcl10+/Mmp14+ monocytes and Ccl3+ neutrophils proactively mediates silica-induced pulmonary fibrosis. Journal of hazardous materials 18 38335607
2019 The role of CXCR3 and its ligands CXCL10 and CXCL11 in the pathogenesis of celiac disease. Medicine 18 31232926
2009 IP-10 protects while MIP-2 promotes experimental anesthetic hapten - induced hepatitis. Journal of autoimmunity 18 19131211
2019 The antiviral protein viperin regulates chondrogenic differentiation via CXCL10 protein secretion. The Journal of biological chemistry 17 30718282
1995 Mob-1 expression in IL-2-induced ARDS: regulation by TNF-alpha. The American journal of physiology 17 8572251
2022 Elevated IP-10 at the Protein and Gene Level Associates With Pulmonary TB. Frontiers in cellular and infection microbiology 16 35694534
2021 The role of IP-10 and its receptor CXCR3 in early pregnancy. Molecular immunology 16 34655920
2018 Plasmacytoid dendritic cell heterogeneity is defined by CXCL10 expression following TLR7 stimulation. Immunology and cell biology 16 29870118
2010 Suppressive effect on MDC and IP-10 expression in monocytes by endocrine disruptor chemicals. Inflammation 16 19756997
2008 Structure of mouse IP-10, a chemokine. Acta crystallographica. Section D, Biological crystallography 16 18560148
2018 Reversing CXCL10 Deficiency Ameliorates Kidney Disease in Diabetic Mice. The American journal of pathology 15 30273603
2006 Mx1 and IP-10: biomarkers to measure IFN-beta activity in mice following gene-based delivery. Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research 15 17032164
2017 Cell autonomous expression of CXCL-10 in JAK2V617F-mutated MPN. Journal of cancer research and clinical oncology 14 28233092

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