Affinage

CXCL9

C-X-C motif chemokine 9 · UniProt Q07325

Length
125 aa
Mass
14.0 kDa
Annotated
2026-06-09
100 papers in source corpus 32 papers cited in narrative 32 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

CXCL9 is an IFN-γ-inducible CXC chemokine that orchestrates the recruitment of activated T lymphocytes to inflamed and tumor tissues by signaling exclusively through the CXCR3 receptor, a G-protein-coupled receptor selectively expressed on IL-2-activated T cells, where ligand binding mobilizes intracellular Ca2+ and drives chemotaxis of activated T cells and tumor-infiltrating lymphocytes while leaving resting T cells, B cells, monocytes, and granulocytes unresponsive (PMID:9064356, PMID:7595201). Its expression is transcriptionally driven by IFN-γ as the primary inducer (PMID:8476424), operating through STAT1 binding to the CXCL9 promoter (PMID:27966526, PMID:26199110) and through NF-κB, which can be engaged by viral HBx protein and is suppressed by nitric oxide donors (PMID:19157479, PMID:11752021); this transcriptional output is repressed by HIF-1α, EZH2, LIF, prostaglandin E2/COX activity, and by M. tuberculosis-mediated displacement of STAT1 from cis-regulatory elements (PMID:21167783, PMID:27490802, PMID:39078728, PMID:38484558, PMID:39702756). Functionally, CXCL9 is non-redundant with the co-receptor ligand CXCL10 in driving antitumor immunity: macrophage-derived CXCL9 is required for CD8+ T cell infiltration and the efficacy of immune checkpoint blockade, and tumors epigenetically silence CXCL9 to escape T cell-mediated control (PMID:31636098, PMID:23241877, PMID:39078728). Beyond leukocyte trafficking, CXCL9 exerts direct, CXCR3-dependent effects on non-immune cells: it is angiostatic by competitively blocking VEGF binding to endothelial cells (PMID:27966526, PMID:31550444), it directly modulates fibrosis—suppressing collagen in hepatic stellate cells and pulmonary arterial smooth muscle cells yet inducing Col1a1 in dermal fibroblasts (PMID:19344719, PMID:36708947, PMID:35763380)—and it skews the Treg/Th17 balance toward Th17 in a JNK-dependent manner (PMID:34461107). CXCL9 also possesses direct antimicrobial activity against bacteria (PMID:27671889). Activity is governed post-translationally by N- and C-terminal proteolysis: C-terminal truncation at basic residues reduces specific activity (PMID:7595201), while DPP-4 cleavage of the two N-terminal residues converts CXCL9 into a CXCR3 competitive antagonist that retains binding but loses receptor activation (PMID:40238455).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1993 Medium

    Establishing what stimulus controls CXCL9 expression was needed to place it in an immune pathway; demonstrating selective IFN-γ inducibility defined it as an interferon-effector chemokine.

    Evidence cDNA screening and Northern blot of IFN-γ-, IFN-α-, and LPS-stimulated human monocytic cells

    PMID:8476424

    Open questions at the time
    • Did not identify the transcription factor mediating IFN-γ induction
    • Single cell type tested
  2. 1995 High

    Whether CXCL9 was a functional chemoattractant with cellular selectivity was unknown; recombinant protein assays showed it triggers Ca2+ flux and chemotaxis in activated/tumor-infiltrating T cells but not neutrophils or monocytes, and that C-terminal truncation tunes its activity.

    Evidence Recombinant CXCL9 from CHO cells, Ca2+ flux, Boyden chamber chemotaxis, SDS-PAGE and N-terminal sequencing

    PMID:7595201

    Open questions at the time
    • Receptor identity not established here
    • Mechanism distinguishing activated from resting T cells unresolved
  3. 1996 High

    The receptor mediating CXCL9 action was unidentified; cloning CXCR3 and showing its selective expression on IL-2-activated T cells defined the receptor basis for CXCL9's leukocyte selectivity.

    Evidence Receptor cloning, Ca2+ flux, chemotaxis, and expression profiling across leukocyte subsets

    PMID:9064356

    Open questions at the time
    • G-protein coupling details not dissected
    • Did not address shared ligand usage with other chemokines
  4. 1997 Medium

    Whether CXCL9 was redundant with CXCL10 and had non-chemotactic functions was open; demonstrating shared CXCR3 usage, reciprocal desensitization, and angiostatic/anti-tumor activity broadened its functional repertoire.

    Evidence Receptor cross-desensitization, in vitro angiogenesis inhibition, and in vivo tumor models

    PMID:9060447

    Open questions at the time
    • Molecular mechanism of angiostasis not defined
    • Degree of non-redundancy with CXCL10 unresolved
  5. 2002 Medium

    Transcriptional control beyond IFN-γ and the cellular source in vivo were unclear; mesangial, cardiac allograft, and viral hepatitis studies identified NF-κB as a co-regulator, macrophages/hepatocytes as sources, and a functionally required role in CD4+ T cell recruitment.

    Evidence EMSA for NF-κB in cytokine-stimulated mesangial cells, antibody neutralization in murine cardiac transplant and adenovirus hepatitis models with immunostaining

    PMID:11752021 PMID:12368204 PMID:12473267

    Open questions at the time
    • Quantitative contribution of NF-κB vs STAT1 not resolved
    • Co-stimulatory Fas requirement mechanism in hepatocytes incompletely defined
  6. 2003 Medium

    Whether CXCL9 cooperated with other chemokines in antitumor immunity was untested; depletion showed it is required alongside CXCL10 for CCL21-driven antitumor responses and CXCR3+ T cell/DC accumulation.

    Evidence In vivo antibody depletion, flow cytometry, and chemokine measurement at the tumor site

    PMID:12740040

    Open questions at the time
    • Single tumor system
    • Did not separate CXCL9-specific from CXCL10-specific contributions
  7. 2009 High

    Direct non-immune cellular actions were unproven; stellate cell assays and CXCR3-KO mice established a direct antifibrotic effect and a Th1-associated antifibrotic axis, while HBx studies mapped NF-κB binding to a defined promoter position.

    Evidence LX-2 collagen assays, CXCR3-KO liver fibrosis model, and luciferase/ChIP/EMSA mapping of NF-κB at MIG promoter -147

    PMID:19157479 PMID:19344719

    Open questions at the time
    • Downstream signaling driving collagen suppression not detailed
    • Direct vs IFN-γ-mediated contributions to the in vivo phenotype not fully separated
  8. 2012 Medium

    Whether CXCL9 was functionally non-redundant in tumor immunity was unsettled; immunoediting models showed tumors epigenetically lose CXCL9 under IFN-γ/T cell pressure and that CXCL10 cannot compensate.

    Evidence Methylcholanthrene fibrosarcoma/melanoma models with T cell and IFN-γ immune stress and chemokine expression analysis

    PMID:23241877

    Open questions at the time
    • Epigenetic mechanism of silencing not molecularly defined
    • Single carcinogen-induced tumor lineage
  9. 2016 High

    The mechanism of angiostasis and additional regulatory inputs were unknown; osteoblast studies showed CXCL9 binds VEGF to block its receptor engagement under mTORC1/STAT1 control, PGE2/COX was identified as a negative regulator, and direct antimicrobial activity was demonstrated.

    Evidence VEGF binding competition assays, STAT1 ChIP, rapamycin inhibition in bone marrow/MSC models, COX inhibitor and ELISA studies, radial diffusion antimicrobial assays

    PMID:27490802 PMID:27671889 PMID:27966526 PMID:31550444

    Open questions at the time
    • Structural basis of CXCL9-VEGF interaction not defined
    • Antimicrobial mechanism (membrane vs receptor) not established
  10. 2018 Medium

    Whether CXCR3 signaling in tumor cells had cell-intrinsic consequences was open; gastric cancer studies showed CXCR3 ligands upregulate PD-L1 via STAT3 and PI3K-Akt.

    Evidence Recombinant CXCL9/10/11 treatment with CXCR3 blocking and pathway western blots in vitro and in vivo

    PMID:29690901

    Open questions at the time
    • CXCL9-specific contribution not isolated from CXCL10/11
    • Single cancer type
  11. 2019 High

    The therapeutically critical cellular source and a key suppressive input were undefined; checkpoint blockade and glucocorticoid studies identified macrophages as the required CXCL9 source for ICB efficacy and renal tubular epithelium as a glucocorticoid-suppressible source.

    Evidence Macrophage depletion with scRNA-seq in murine and human tumor data; cell-type-specific glucocorticoid treatment in renal tubular cells and crescentic glomerulonephritis models

    PMID:31636098 PMID:36355429

    Open questions at the time
    • Transcriptional program distinguishing macrophage CXCL9 induction not fully mapped
    • Glucocorticoid target elements on CXCL9 promoter not defined
  12. 2022 High

    The breadth of context-specific fibrotic and immune-modulatory effects was unresolved; KO and gain/loss studies defined CXCL9 as directly pro-fibrotic in skin (Col1a1 induction) yet antifibrotic in lung smooth muscle, a Th17-skewing factor via JNK, and an enabler of antitumor responses in ovarian cancer.

    Evidence Cxcl9/Cxcr3-KO bleomycin skin and PH/fibrosis models, NKT coculture, AAV silencing in MASH with phospho-JNK readouts, CXCL9 overexpression in ovarian cancer models

    PMID:34461107 PMID:35314795 PMID:35763380 PMID:36708947

    Open questions at the time
    • Tissue-specific determinants of pro- vs antifibrotic outcome unexplained
    • JAK1/STAT2 activation in breast cancer cells rests on a single western-blot study without receptor knockdown (low confidence)
  13. 2024 High

    Post-translational and upstream transcriptional control of CXCL9 activity required clarification; DPP-4 was shown to convert CXCL9 to a CXCR3 antagonist by N-terminal cleavage, and HIF-1α, EZH2, and LIF were identified as repressors whose targeting restores CXCL9 and CD8+ T cell infiltration.

    Evidence DPP-4 cleavage and CXCR3 binding/activation assays with N-terminal glutamine engineering; HIF-1α and EZH2 knockdown/overexpression with CXCR3 neutralization; LIF blockade in syngeneic and patient-derived tumor models

    PMID:38484558 PMID:39078728 PMID:39702756 PMID:40238455

    Open questions at the time
    • In vivo extent of DPP-4-mediated CXCL9 antagonism not quantified
    • Hierarchy among HIF-1α, EZH2, and LIF repression in a given tumor not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CXCL9 produces opposite fibrotic outcomes in different tissues through a single CXCR3 receptor, and the structural/signaling determinants distinguishing its angiostatic VEGF-sequestering function from its chemotactic GPCR signaling, remain unresolved.
  • No structural model of CXCL9-CXCR3 vs CXCL9-VEGF interaction
  • Cell-context-dependent CXCR3 signaling branches not mechanistically separated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 3 GO:0048018 receptor ligand activity 2 GO:0060089 molecular transducer activity 2
Localization
GO:0005576 extracellular region 3
Pathway
R-HSA-1500931 Cell-Cell communication 3 R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 3
Partners
CXCR3DPP4VEGFA

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 CXCL9 (Mig) signals through the CXCR3 receptor, a G-protein coupled receptor selectively expressed on IL-2-activated T lymphocytes; binding mediates Ca2+ mobilization and chemotaxis specifically in activated T cells but not in resting T cells, B cells, monocytes, or granulocytes. Receptor cloning, Ca2+ flux assay, chemotaxis assay, expression profiling by Northern/flow cytometry The Journal of experimental medicine High 9064356
1995 Recombinant human CXCL9 (Mig) induces transient elevation of intracellular Ca2+ and is chemotactic for activated T lymphocytes and tumor-infiltrating lymphocytes, but not for neutrophils or monocytes; secreted CXCL9 exists as multiple species due to proteolytic cleavage at basic carboxy-terminal residues occurring intracellularly before secretion, and carboxy-terminal truncation reduces specific activity. CHO cell expression/purification, Ca2+ flux assay, modified Boyden chamber chemotaxis assay, SDS-PAGE, N-terminal sequencing The Journal of experimental medicine High 7595201
1993 CXCL9 (HuMig) is induced in human monocytic cells (THP-1) and peripheral blood mononuclear cells by IFN-γ but not by IFN-α or LPS, establishing IFN-γ as the primary transcriptional inducer. cDNA library screening, Northern blot, cytokine stimulation assays Biochemical and biophysical research communications Medium 8476424
1997 CXCL9 and IP-10/CXCL10 share the CXCR3 receptor, show reciprocal desensitization on activated T cells, inhibit neovascularization, inhibit hematopoietic progenitor cells, and exert anti-tumor effects in vitro and in vivo. Receptor cross-desensitization assay, in vitro angiogenesis inhibition assay, in vivo tumor models Journal of leukocyte biology Medium 9060447
2009 CXCL9 exerts direct antifibrotic effects on human hepatic stellate cells (LX-2) by suppressing collagen production; CXCR3-deficient mice show increased liver fibrosis associated with decreased intrahepatic IFN-γ-positive T cells and reduced IFN-γ mRNA, indicating that CXCL9-CXCR3 regulates Th1-associated antifibrotic immune pathways in the liver. In vitro stellate cell stimulation (collagen production assay), CXCR3 knockout mouse model of liver fibrosis, intrahepatic immune cell subset analysis, IFN-γ mRNA measurement Gastroenterology High 19344719
2016 Osteoblast-secreted CXCL9 acts as an angiostatic factor by interacting with VEGF and preventing its binding to endothelial cells and osteoblasts, thereby abrogating angiogenesis and osteogenesis in bone marrow; mTORC1 activates CXCL9 expression in osteoblasts by transcriptional upregulation of STAT1, which increases STAT1 binding to the Cxcl9 promoter. Mouse bone marrow model, in vitro VEGF binding competition assay, STAT1 ChIP assay, mTORC1 signaling inhibition Nature communications High 27966526
2002 CXCL9 (MIG) plays a functionally required role in CD4+ T lymphocyte recruitment in cardiac allograft vasculopathy (CAV); macrophages (MOMA-2+) are the predominant source of CXCL9 in this context, and antibody neutralization of CXCL9 significantly reduces CD4+ T cell infiltration and intimal thickening. MHC II-mismatched murine cardiac transplant model, antibody neutralization, immunohistochemistry, gene expression profiling The American journal of pathology High 12368204
2003 CXCL9 (MIG) and CXCL10 (IP-10) are required for SLC/CCL21-mediated antitumor responses; in vivo depletion of either chemokine reduces antitumor efficacy, CXCR3+ T cell frequency, and CD11c+ DC accumulation at the tumor site, revealing interdependence among IFN-γ, CXCL9, and CXCL10 in antitumor immunity. In vivo antibody depletion/neutralization, flow cytometry, cytokine/chemokine measurement at tumor site Molecular cancer Medium 12740040
2009 Hepatitis B virus HBx protein induces CXCL9 (MIG) expression in a dose-dependent manner via direct NF-κB binding to the MIG promoter at position -147, as demonstrated by luciferase reporter, ChIP, and EMSA; increased CXCL9 protein levels enhance migration of peripheral blood lymphocytes, an effect blocked by NF-κB inhibition. Luciferase reporter assay, chromatin immunoprecipitation (ChIP), electrophoretic mobility shift assay (EMSA), chemotaxis assay, NF-κB inhibition Virology High 19157479
2002 In the virus-infected liver (adenovirus hepatitis model), IFN-γ induces CXCL9 (MIG) and IP-10 in hepatocytes; optimal induction requires a co-stimulatory signal from Fas cross-linking on hepatocytes; NK/T cells expressing NK1.1 and AsGM1 provide both signals; antibody-mediated ablation of NK/T cells inhibits IFN-γ and chemokine transcript induction. T cell (but not NK cell) chemotaxis by hepatocyte supernatants was abrogated by anti-Mig and anti-Crg-2 antibodies. Murine adenovirus hepatitis model, NK/T cell depletion, anti-Fas antibody injection, neutralizing antibody chemotaxis inhibition assay Cellular immunology Medium 12473267
2002 IFN-γ plus TNF-α induces CXCL9 (MIG) expression in human mesangial cells; NO donors suppress this induction through cGMP-independent inhibition of NF-κB activation, as shown by EMSA. Primary human mesangial cell culture, cytokine stimulation, EMSA, NO donor treatment, immunostaining Journal of the American Society of Nephrology : JASN Medium 11752021
1999 CXCL9 (MIG) and CXCL10 (IP-10), signaling through CXCR3 expressed on mesangial cells, directly induce proliferation of human mesangial cells, revealing a non-immune direct cellular effect of these chemokines. CXCR3 expression by flow cytometry, Ca2+ flux assay, cell proliferation assay with recombinant chemokines Journal of the American Society of Nephrology : JASN Medium 10589690
2010 M. tuberculosis inhibits IFN-γ-induced CXCL9 (MIG) transcription by disrupting STAT1α binding to cis-regulatory elements in the MIG promoter, partially via NF-κB and p38 MAPK pathways; paradoxically, combined IFN-γ and MTB stimulation increases MIG protein through post-transcriptional mechanisms involving NF-κB and p38 MAPK. STAT1 EMSA on MIG promoter elements, kinase inhibitor studies, RT-PCR, ELISA protein measurement Tuberculosis (Edinburgh, Scotland) Medium 21167783
2016 Progranulin (PGRN) inhibits TNF- and IFN-γ-induced CXCL9 and CXCL10 expression, and this inhibitory effect depends on TNFR1 signaling, as demonstrated by gene array analysis in PGRN-null mice and recombinant PGRN protein treatment experiments. Gene array on PGRN KO vs. WT CD4+ T cells, recombinant PGRN treatment, TNFR1-dependent rescue experiments, dermatitis model Scientific reports Medium 26892362
2015 IL-27 induces CXCL9, CXCL10, and CXCL11 expression in hepatic cells in a STAT1-dependent manner; during ConA-induced hepatitis, IL-27 and IFN-γ cooperatively regulate CXCR3 ligand expression, with IFN-γ KO abolishing upregulation. In vitro cytokine stimulation (human hepatic cell lines and primary cells), in vivo ConA hepatitis model, IL-27 neutralization, IFN-γ KO mice, RT-PCR, ELISA Journal of molecular medicine (Berlin, Germany) Medium 26199110
2019 Macrophages are the predominant cellular source of CXCL9 following dual PD-1/CTLA-4 immune checkpoint blockade; macrophage depletion abrogates CD8+ T cell infiltration and therapeutic efficacy, establishing macrophage-derived CXCL9 as functionally required for ICB antitumor responses. NanoString analysis, flow cytometry, cytometric bead array, antibody depletion, single-cell RNA-seq, murine tumor models Clinical cancer research High 31636098
2022 CXCL9 directly induces Col1a1 (collagen type I) mRNA expression in murine fibroblasts via CXCR3; fibrosis in a bleomycin skin model is dependent on CXCL9 and CXCR3 (not CXCL10), as shown by chemokine- and receptor-deficient mouse experiments. Cxcl9-KO, Cxcl10-KO, Cxcr3-KO mouse bleomycin fibrosis model, recombinant CXCL9 stimulation of fibroblasts, Col1a1 mRNA quantification, REX3 reporter mice The Journal of investigative dermatology High 36708947
2022 CXCL9 promotes Th17 cell proliferation and skews the Treg/Th17 balance toward Th17 in a JNK-dependent manner; AAV-mediated silencing of CXCL9 in a murine MASH model reduces Th17 frequency and phospho-JNK levels, while CXCL9 overexpression has the opposite effect. Recombinant adeno-associated virus gene transfer/silencing, T cell differentiation assays, phospho-JNK western blot, JNK inhibitor experiments, murine MASH model Experimental cell research Medium 34461107
2022 CXCL9 signaling through CXCR3 activates the JAK1/STAT2 pathway in triple-negative breast cancer cells; CXCL9 overexpression increases JAK1/STAT2 phosphorylation as shown by western blot. CXCL9 overexpression in MDA-MB-231 cells, western blot for JAK1/STAT2 phosphorylation Cancer immunology, immunotherapy : CII Low 36472587
2018 CXCL9/10/11 signaling through CXCR3 upregulates PD-L1 expression in gastric cancer cells by activating STAT3 and Akt (PI3K-Akt) pathways; blocking CXCR3 signaling abolishes PD-L1 upregulation and phosphorylation of STAT3 and Akt. Western blot, gastric cancer cell line treatment with recombinant CXCL9/10/11, CXCR3 blocking, in vivo tumor experiments BMC cancer Medium 29690901
2022 CXCL9 overexpression in murine ovarian cancer (ID8) models results in T-cell accumulation, delayed ascites formation, and improved survival dependent on adaptive immune function; in ICB-resistant models, CXCL9 is sufficient to enable successful anti-PD-L1 therapy. Murine ovarian cancer models with CXCL9 overexpression, immune depletion experiments, survival analysis, flow cytometry British journal of cancer Medium 35314795
2022 CXCL9 inhibits collagen deposition in human pulmonary arterial smooth muscle cells (hPASMCs) via CXCR3, and pharmacological NKT cell activation restores CXCL9 production and ameliorates vascular remodeling in a mouse PH/fibrosis model via the STAT1-CXCL9-CXCR3 axis; CXCL10 did not share this antifibrotic effect. NKT cell coculture with hPASMCs, secretome analysis, CXCL9 recombinant protein treatment, CXCR3 inhibition, murine PH/fibrosis model with pharmacological NKT activation (KRN7000) American journal of respiratory and critical care medicine Medium 35763380
2016 Prostaglandin E2 (a COX metabolite) acts as a negative regulator of CXCL9 secretion in ovarian cancer cell lines, while COX inhibition by indomethacin (but not celecoxib) significantly upregulates CXCL9; celecoxib suppresses NF-κB activation and inhibits CXCL9 release. Ovarian cancer cell line treatment with PGE2 and COX inhibitors, ELISA for CXCL9/CXCL10, NF-κB activation assay British journal of cancer Medium 27490802
2024 DPP-4 cleaves the two N-terminal amino acids of CXCL9, converting it into a CXCR3 competitive antagonist that retains binding but loses receptor activation; adding an N-terminal glutamine residue to CXCL9-Fc renders it a fully active CXCR3 agonist resistant to DPP-4 cleavage, as demonstrated by biochemical analysis and computational modeling. Biochemical DPP-4 cleavage assay, CXCR3 binding and activation assays, computational modeling, engineering of N-terminal glutamine variant Proceedings of the National Academy of Sciences of the United States of America High 40238455
2012 IFN-γ-mediated immune stress imposed by T cells drives tumor cells to epigenetically lose CXCL9/Mig expression (immunoediting); Mig-deficient tumor variants show increased resistance to T cell-mediated immunity; CXCL10 expression does not compensate for absent CXCL9 antitumor function, indicating a non-redundant role for CXCL9. Methylcholanthrene-induced fibrosarcoma and melanoma models, in vivo T cell and IFN-γ immune stress experiments, chemokine expression analysis, tumor growth assays Journal of immunology (Baltimore, Md. : 1950) Medium 23241877
2019 Glucocorticoids suppress CXCL9 and CXCL10 expression directly in renal tubular epithelial cells (not in T cells), resulting in reduced CXCR3+CD4+ T cell recruitment to the inflamed kidney; this CXCL9/CXCL10-CXCR3 axis was identified as a target of glucocorticoid-mediated protection in crescentic glomerulonephritis. In vitro glucocorticoid treatment of renal tubular cells, experimental mouse crescentic glomerulonephritis model, single-cell analysis of kidney biopsies, T cell recruitment assays JCI insight Medium 36355429
2019 Cxcl9 secreted by osteoblasts during osteogenic differentiation in MSC co-cultures inhibits angiogenesis by suppressing VEGF binding to endothelial cells; mTOR/STAT1 signaling activates Cxcl9 in osteoblasts; blocking this pathway with rapamycin reduces Cxcl9 and restores angiogenesis. MSC-HUVEC co-culture, VEGF binding assay, mTOR/STAT1 inhibition with rapamycin, Cxcl9 knockdown Archives of biochemistry and biophysics Medium 31550444
2024 CXCL9, CXCL10, and CCL19 are synergistically required for T cell (CD8+) recruitment in lichen planus; keratinocytes and fibroblasts in LP lesions are identified as cellular sources; an in vitro migration assay demonstrated synergistic enhancement of CD8+ T cell recruitment by CCL19 combined with CXCL9 or CXCL10 beyond any individual cytokine. scRNA-seq on blood and skin, in vitro T cell migration assay with primary human T cells and recombinant cytokines JCI insight Medium 39190494
2024 LIF (leukemia inhibitory factor) induced by HPV E6/E7 via NFκB suppresses CXCL9 expression in tumor-associated macrophages; LIF blockade promotes CXCL9 induction and CD8+ T cell infiltration, sensitizing tumors to immune checkpoint inhibitors. Primary pDC and macrophage cultures, LIF blockade experiments, syngeneic animal models, patient-derived models, flow cytometry for CD8+ T cells Clinical cancer research Medium 39078728
2024 HIF-1α suppresses CXCL9 (and CXCL10, CXCL11) expression in colorectal cancer; HIF-1α knockdown or overexpression respectively increases or decreases these chemokines in vitro; in vivo BIRC2/HIF-1α inhibition promotes CD8+ T cell infiltration via the CXCL9/CXCL10/CXCL11-CXCR3 axis, and this is reversed by CXCR3 neutralization. HIF-1α knockdown/overexpression in CRC cell lines, CXCR3 neutralizing antibody in vivo, xenograft/syngeneic mouse models, flow cytometry Biomedicine & pharmacotherapy Medium 38484558
2024 EZH2 in tumor cells suppresses CXCL9 expression by repressing NF-κB-mediated CXCL9 transcriptional activation; EZH2 targeting restores CXCL9 expression and enhances CD8+ T cell infiltration into the tumor microenvironment of esophageal squamous cell carcinoma. EZH2 KD/inhibition, NF-κB pathway analysis, CXCL9 promoter regulation, CD8+ T cell infiltration assays in vivo and in vitro Communications biology Medium 39702756
2016 CXCL9 has direct antimicrobial activity against Streptococcus sanguinis and E. coli as demonstrated by radial diffusion assay; CXCL9 mRNA is absent in unstimulated oral keratinocytes but strongly induced by IFN-γ, whereas CXCL10 is constitutively expressed and enhanced by LPS. Radial diffusion antimicrobial assay, mRNA expression profiling by PCR with various stimuli (IFN-γ, LPS) European journal of oral sciences Medium 27671889

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
1996 Chemokine receptor specific for IP10 and mig: structure, function, and expression in activated T-lymphocytes. The Journal of experimental medicine 976 9064356
1997 Mig and IP-10: CXC chemokines that target lymphocytes. Journal of leukocyte biology 655 9060447
2019 Macrophage-Derived CXCL9 and CXCL10 Are Required for Antitumor Immune Responses Following Immune Checkpoint Blockade. Clinical cancer research : an official journal of the American Association for Cancer Research 590 31636098
2023 CXCL9:SPP1 macrophage polarity identifies a network of cellular programs that control human cancers. Science (New York, N.Y.) 491 37535729
1995 Human Mig chemokine: biochemical and functional characterization. The Journal of experimental medicine 315 7595201
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
2016 CXCL9 and CXCL10 predict survival and are regulated by cyclooxygenase inhibition in advanced serous ovarian cancer. British journal of cancer 220 27490802
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
1993 HuMig: a new human member of the chemokine family of cytokines. Biochemical and biophysical research communications 164 8476424
2007 The MIG-2/integrin interaction strengthens cell-matrix adhesion and modulates cell motility. The Journal of biological chemistry 150 17513299
2009 Antifibrotic effects of CXCL9 and its receptor CXCR3 in livers of mice and humans. Gastroenterology 143 19344719
2016 Osteoblasts secrete Cxcl9 to regulate angiogenesis in bone. Nature communications 124 27966526
2006 Evidence that MIG-6 is a tumor-suppressor gene. Oncogene 109 16819504
2006 MIG-10/lamellipodin and AGE-1/PI3K promote axon guidance and outgrowth in response to slit and netrin. Current biology : CB 107 16618541
1989 Growth and differentiation of a human megakaryoblastic cell line, CMK. Blood 105 2665839
2021 CXCL9-expressing tumor-associated macrophages: new players in the fight against cancer. Journal for immunotherapy of cancer 104 33637602
1999 Role for interactions between IP-10/Mig and CXCR3 in proliferative glomerulonephritis. Journal of the American Society of Nephrology : JASN 102 10589690
2010 Mig-6 controls EGFR trafficking and suppresses gliomagenesis. Proceedings of the National Academy of Sciences of the United States of America 99 20351267
2024 CXCL9/10-engineered dendritic cells promote T cell activation and enhance immune checkpoint blockade for lung cancer. Cell reports. Medicine 87 38518770
2009 Mig-6 modulates uterine steroid hormone responsiveness and exhibits altered expression in endometrial disease. Proceedings of the National Academy of Sciences of the United States of America 82 19439667
2018 CXCL9/10/11, a regulator of PD-L1 expression in gastric cancer. BMC cancer 78 29690901
2002 IP-10 and Mig production by glomerular cells in human proliferative glomerulonephritis and regulation by nitric oxide. Journal of the American Society of Nephrology : JASN 78 11752021
2007 Mig-6, signal transduction, stress response and cancer. Cell cycle (Georgetown, Tex.) 76 17351343
2011 Dysregulated expression of MIG/CXCL9, IP-10/CXCL10 and CXCL16 and their receptors in systemic sclerosis. Arthritis research & therapy 72 21303517
2016 Interleukin-6, MCP-1, IP-10, and MIG are sequentially expressed in cerebrospinal fluid after subarachnoid hemorrhage. Journal of neuroinflammation 67 27576738
2003 SLC/CCL21-mediated anti-tumor responses require IFNgamma, MIG/CXCL9 and IP-10/CXCL10. Molecular cancer 66 12740040
2022 CXCL9 inhibits tumour growth and drives anti-PD-L1 therapy in ovarian cancer. British journal of cancer 61 35314795
2023 Identification and validation of urinary CXCL9 as a biomarker for diagnosis of acute interstitial nephritis. The Journal of clinical investigation 60 37395276
2018 AC-YVAD-CMK Inhibits Pyroptosis and Improves Functional Outcome after Intracerebral Hemorrhage. BioMed research international 55 30410928
2019 CXCR3-CXCL9: It's All in the Tumor. Immunity 53 31216458
2002 The role of MIG/CXCL9 in cardiac allograft vasculopathy. The American journal of pathology 52 12368204
2017 Tissue-specific regulation of CXCL9/10/11 chemokines in keratinocytes: Implications for oral inflammatory disease. PloS one 51 28253295
2024 The IFN-γ-CXCL9/CXCL10-CXCR3 axis in vitiligo: Pathological mechanism and treatment. European journal of immunology 50 37937817
2022 Impairment of the NKT-STAT1-CXCL9 Axis Contributes to Vessel Fibrosis in Pulmonary Hypertension Caused by Lung Fibrosis. American journal of respiratory and critical care medicine 49 35763380
2002 IP-10 and Mig facilitate accumulation of T cells in the virus-infected liver. Cellular immunology 49 12473267
2017 Transcriptional and Cytokine Profiles Identify CXCL9 as a Biomarker of Disease Activity in Morphea. The Journal of investigative dermatology 46 28450066
2012 Cancer-type regulation of MIG-6 expression by inhibitors of methylation and histone deacetylation. PloS one 45 22701735
2022 CXCL9-modified CAR T cells improve immune cell infiltration and antitumor efficacy. Cancer immunology, immunotherapy : CII 41 35352167
2013 IP-10/CXCL10 and MIG/CXCL9 as novel markers for the diagnosis of lymphoma-associated hemophagocytic syndrome. Annals of hematology 41 23975214
2020 The Multifaceted Roles of CXCL9 Within the Tumor Microenvironment. Advances in experimental medicine and biology 39 32060845
2003 Increased IP-10 and MIG expression after intra-amniotic endotoxin in preterm lamb lung. American journal of respiratory and critical care medicine 39 12598219
2008 Regulation of CXCL9/10/11 in oral keratinocytes and fibroblasts. Journal of dental research 38 19029086
2022 Loss of MIG-6 results in endometrial progesterone resistance via ERBB2. Nature communications 37 35232969
2020 CXCL9 chemokine promotes the progression of human pancreatic adenocarcinoma through STAT3-dependent cytotoxic T lymphocyte suppression. Aging 37 31913856
2020 Targeted Delivery of CXCL9 and OX40L by Mesenchymal Stem Cells Elicits Potent Antitumor Immunity. Molecular therapy : the journal of the American Society of Gene Therapy 37 32827461
2019 The Role of CXCL13 and CXCL9 in Early Breast Cancer. Clinical breast cancer 37 31699671
2019 Ac-YVAD-cmk improves neurological function by inhibiting caspase-1-mediated inflammatory response in the intracerebral hemorrhage of rats. International immunopharmacology 36 31352322
2016 Progranulin inhibits expression and release of chemokines CXCL9 and CXCL10 in a TNFR1 dependent manner. Scientific reports 36 26892362
2009 HBx protein induces expression of MIG and increases migration of leukocytes through activation of NF-kappaB. Virology 36 19157479
2022 CXCL9 influences the tumor immune microenvironment by stimulating JAK/STAT pathway in triple-negative breast cancer. Cancer immunology, immunotherapy : CII 33 36472587
2019 CXCL9 and CXCL10 are differentially associated with systemic organ involvement and pulmonary disease severity in sarcoidosis. Respiratory medicine 31 31783271
2021 Highly Sensitive Immuno-CRISPR Assay for CXCL9 Detection. Analytical chemistry 30 34865465
2001 Primary hepatocytes from mice treated with IL-2/IL-12 produce T cell chemoattractant activity that is dependent on monokine induced by IFN-gamma (Mig) and chemokine responsive to gamma-2 (Crg-2). Journal of immunology (Baltimore, Md. : 1950) 29 11238618
2021 MIG/CXCL9 exacerbates the progression of metabolic-associated fatty liver disease by disrupting Treg/Th17 balance. Experimental cell research 28 34461107
2020 Effective Treatments for Bladder Cancer Affecting CXCL9/CXCL10/CXCL11/CXCR3 Axis: A Review. Oman medical journal 28 32181005
2018 CXCL9 chemokine in ulcerative colitis. La Clinica terapeutica 28 30393811
2017 HPV16E7-Induced Hyperplasia Promotes CXCL9/10 Expression and Induces CXCR3+ T-Cell Migration to Skin. The Journal of investigative dermatology 26 29277541
2022 CXCL8, CXCL9, CXCL10, and CXCL11 as biomarkers of liver injury caused by chronic hepatitis B. Frontiers in microbiology 25 36504808
2015 Interleukin-27 and IFNγ regulate the expression of CXCL9, CXCL10, and CXCL11 in hepatitis. Journal of molecular medicine (Berlin, Germany) 25 26199110
2024 Interferon-gamma driven elevation of CXCL9: a new sepsis endotype independently associated with mortality. EBioMedicine 23 39447386
2015 MIG-7 and phosphorylated prohibitin coordinately regulate lung cancer invasion/metastasis. Oncotarget 23 25575814
2024 CXCL9, CXCL10, and CCL19 synergistically recruit T lymphocytes to skin in lichen planus. JCI insight 22 39190494
2006 mig-5/Dsh controls cell fate determination and cell migration in C. elegans. Developmental biology 22 16899238
2023 CXCL9 Links Skin Inflammation and Fibrosis through CXCR3-Dependent Upregulation of Col1a1 in Fibroblasts. The Journal of investigative dermatology 20 36708947
2019 Urinary CXCL9 and CXCL10 Levels and Acute Renal Graft Rejection. International journal of organ transplantation medicine 20 31285802
2017 A MIG-15/JNK-1 MAP kinase cascade opposes RPM-1 signaling in synapse formation and learning. PLoS genetics 20 29228003
2013 Differential expression of CXCL1, CXCL9, CXCL10 and CXCL12 chemokines in alopecia areata. Iranian journal of immunology : IJI 19 23502337
2012 MIG-10 functions with ABI-1 to mediate the UNC-6 and SLT-1 axon guidance signaling pathways. PLoS genetics 19 23209429
2011 MIG-15 and ERM-1 promote growth cone directional migration in parallel to UNC-116 and WVE-1. Development (Cambridge, England) 19 21937599
2020 CXCL9 Predicts Severity at the Onset of Chronic Graft-versus-host Disease. Transplantation 18 31929430
2012 Cutaneous tumors cease CXCL9/Mig production as a result of IFN-γ-mediated immunoediting. Journal of immunology (Baltimore, Md. : 1950) 17 23241877
2006 Tanacetum parthenium and Salix alba (Mig-RL) combination in migraine prophylaxis: a prospective, open-label study. Clinical drug investigation 17 17163262
2024 Cervical Cancer Evades the Host Immune System through the Inhibition of Type I Interferon and CXCL9 by LIF. Clinical cancer research : an official journal of the American Association for Cancer Research 16 39078728
2023 Glucocorticoids target the CXCL9/CXCL10-CXCR3 axis and confer protection against immune-mediated kidney injury. JCI insight 16 36355429
2017 MIG-6 negatively regulates STAT3 phosphorylation in uterine epithelial cells. Oncogene 16 28925396
2013 Expression of CXCR3 and its ligands CXCL9, -10 and -11 in paediatric opsoclonus-myoclonus syndrome. Clinical and experimental immunology 16 23600831
2023 CXCL9 and its Receptor CXCR3, an Important Link Between Inflammation and Cardiovascular Risks in RA Patients. Inflammation 15 37542661
2016 The CaM Kinase CMK-1 Mediates a Negative Feedback Mechanism Coupling the C. elegans Glutamate Receptor GLR-1 with Its Own Transcription. PLoS genetics 15 27462879
2024 HIF-1α Mediates Immunosuppression and Chemoresistance in Colorectal Cancer by Inhibiting CXCL9, -10 and -11. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 14 38484558
2023 Ac-YVAD-cmk ameliorated sevoflurane-induced cognitive dysfunction and revised mitophagy impairment. PloS one 14 36696410
2021 Ac-FLTD-CMK inhibits pyroptosis and exerts neuroprotective effect in a mice model of traumatic brain injury. Neuroreport 14 33470761
2016 Antimicrobial activity and regulation of CXCL9 and CXCL10 in oral keratinocytes. European journal of oral sciences 14 27671889
2015 CXCL9 and CXCL10 gene polymorphisms in patients with rheumatoid arthritis. Rheumatology international 14 25702175
2015 Mig-6 regulates endometrial genes involved in cell cycle and progesterone signaling. Biochemical and biophysical research communications 14 25976672
2025 Development of DPP-4-resistant CXCL9-Fc and CXCL10-Fc chemokines for effective cancer immunotherapy. Proceedings of the National Academy of Sciences of the United States of America 13 40238455
2020 Suppression of Mig-6 overcomes the acquired EGFR-TKI resistance of lung adenocarcinoma. BMC cancer 13 32552717
2024 Pharmacological Polarization of Tumor-Associated Macrophages Toward a CXCL9 Antitumor Phenotype. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 12 38342608
2024 Microwave ablation combined with PD-L1 blockade synergistically promotes Cxcl9-mediated antitumor immunity. Cancer science 12 38655660
2022 CXCL9-11 chemokines and CXCR3 receptor in teleost fish species. Fish and shellfish immunology reports 12 36569039
2010 Mycobacterium tuberculosis increases IP-10 and MIG protein despite inhibition of IP-10 and MIG transcription. Tuberculosis (Edinburgh, Scotland) 12 21167783
2003 Expression of the Mig (CXCL9) gene in murine lung carcinoma cells generated angiogenesis-independent antitumor effects. Oncology reports 12 12792744
2024 EZH2 elicits CD8+ T-cell desert in esophageal squamous cell carcinoma via suppressing CXCL9 and dendritic cells. Communications biology 11 39702756
2023 EBV-positive pyothorax-associated lymphoma expresses CXCL9 and CXCL10 chemokines that attract cytotoxic lymphocytes via CXCR3. Cancer science 11 36898851
2021 Polymorphisms in CXCR3 ligands predict early CXCL9 recovery and severe chronic GVHD. Blood cancer journal 11 33640906
2019 Inhibiting expression of Cxcl9 promotes angiogenesis in MSCs-HUVECs co-culture. Archives of biochemistry and biophysics 11 31550444
2019 Rheumatoid arthritis and the Th1 chemokine MIG. La Clinica terapeutica 11 31696912
2018 MIG-6 suppresses endometrial epithelial cell proliferation by inhibiting phospho-AKT. BMC cancer 11 29843645
2017 Mig-6 Mouse Model of Endometrial Cancer. Advances in experimental medicine and biology 11 27910070
2013 MIG: Multi-Image Genome viewer. Bioinformatics (Oxford, England) 11 23842811

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