Affinage

LGALS9

Galectin-9 · UniProt O00182

Round 2 corrected
Length
355 aa
Mass
39.5 kDa
Annotated
2026-04-28
56 papers in source corpus 28 papers cited in narrative 28 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

Galectin-9 is a tandem-repeat β-galactoside-binding lectin that functions as a pleiotropic immunomodulator, shaping adaptive and innate immunity through engagement of multiple cell-surface receptors and an intracellular role in autophagy regulation. Secreted galectin-9 is the canonical ligand for TIM-3, triggering Th1 cell apoptosis via a Ca²⁺–calpain–caspase-1 cascade (PMID:16286920, PMID:12646627), and also binds PD-1, where PD-1 co-engagement attenuates TIM-3-mediated killing and sustains exhausted T-cell persistence (PMID:33547304); additionally, it ligates Dectin-1 on macrophages to drive tolerogenic programming in pancreatic cancer (PMID:28394331), and binds cell-surface protein disulfide isomerase to modulate Th2 migration and redox status (PMID:21670307). Tumor-derived exosomal galectin-9 suppresses antitumor immunity by inhibiting dendritic-cell antigen presentation (PMID:33093453, PMID:19005181), while an autocrine TIM-3/galectin-9 loop co-activates NF-κB and β-catenin to promote leukemia stem-cell self-renewal (PMID:26279267); intracellularly, galectin-9 acts as a lysosomal inhibitor that blocks autophagosome–lysosome fusion, selectively killing KRAS-mutant colorectal cancer cells through frustrated autophagy (PMID:26086204).

Mechanistic history

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

    Molecular cloning established that LGALS9 encodes a tandem-repeat galectin with two carbohydrate-recognition domains capable of β-galactoside binding, defining the protein's fundamental biochemical identity.

    Evidence cDNA cloning, recombinant expression in CHO cells, lactose/galactose affinity chromatography

    PMID:9045665

    Open questions at the time
    • Three-dimensional structure of full-length tandem-repeat protein not resolved
    • Relative affinities of N- and C-terminal CRDs for complex glycans not defined
  2. 1998 High

    Discovery that a galectin-9 splice variant (ecalectin) acts as a selective eosinophil chemoattractant revealed that galectin-9 has direct leukocyte-recruiting activity independent of its later-identified Tim-3 pathway.

    Evidence Recombinant ecalectin in COS/insect cells, in vitro and in vivo eosinophil chemotaxis assays

    PMID:9642261

    Open questions at the time
    • Receptor mediating eosinophil chemotaxis not identified
    • Mechanism of non-classical secretion not established
  3. 2003 High

    Pharmacological dissection showed galectin-9 induces T-cell apoptosis through a Ca²⁺–calpain–caspase-1 pathway, distinguishing this death mechanism from classical caspase-8/9-dependent apoptosis.

    Evidence T-cell death assays with selective caspase, calpain, and calcium inhibitors; lactose competition

    PMID:12646627

    Open questions at the time
    • Direct calpain substrates downstream of galectin-9 not identified
    • Tim-3 dependence not yet tested (predates Tim-3 identification as the receptor)
  4. 2005 High

    Identification of galectin-9 as the endogenous ligand for TIM-3 on Th1 cells unified the eosinophil/apoptosis activities under a receptor-mediated framework and established the TIM-3/galectin-9 axis as an immune checkpoint.

    Evidence In vitro binding, calcium flux, Tim-3-deficient cell controls, in vivo depletion of IFN-γ+ cells in autoimmune models

    PMID:16286920

    Open questions at the time
    • Whether Tim-3 is the sole apoptosis-inducing receptor or other receptors contribute remained unclear
    • Structural basis of galectin-9/Tim-3 interaction not determined
  5. 2006 High

    Demonstration that EBV-infected tumor cells package galectin-9 into exosomes that retain Tim-3-binding and T-cell-inhibitory capacity revealed a paracrine immune-evasion mechanism, later confirmed in patient plasma and extended to glioblastoma-derived CSF exosomes.

    Evidence Exosome purification from NPC cell lines and patient plasma, antibody blockade, DC/T-cell functional assays, in vivo knockdown (GBM model)

    PMID:17156439 PMID:19005181 PMID:33093453

    Open questions at the time
    • Sorting mechanism for galectin-9 loading into exosomes not defined
    • Relative contribution of exosomal versus soluble galectin-9 to immune suppression in vivo not quantified
  6. 2010 High

    Genetic epistasis experiments using Tim-3-overexpressing and Gal-9-overexpressing transgenic mice showed that the Tim-3/galectin-9 axis expands granulocytic MDSCs, broadening the pathway's immunosuppressive scope beyond direct T-cell killing.

    Evidence Tim-3-OE × Gal-9-OE double-transgenic and Tim-3-KO rescue crosses, flow cytometry, tumor models

    PMID:20574007

    Open questions at the time
    • Signaling cascade from Tim-3 in myeloid cells driving MDSC expansion not mapped
    • Whether MDSC expansion is cell-intrinsic or indirect not resolved
  7. 2011 High

    Identification of cell-surface protein disulfide isomerase (PDI) as a galectin-9 receptor on Th2 cells revealed a Tim-3-independent pathway linking galectin-9 to redox regulation, β3-integrin-mediated migration, and HIV entry.

    Evidence Surface binding assays, PDI retention measurements, migration and HIV infection assays comparing Th1/Th2 cells

    PMID:21670307

    Open questions at the time
    • Glycan moieties on PDI mediating galectin-9 binding not characterized
    • Relative physiological importance of PDI versus Tim-3 pathway on Th2 cells unknown
  8. 2012 High

    Tim-3 was shown to function as a co-stimulatory receptor for galectin-9 on NK cells (activating ERK and NF-κB to enhance IFN-γ), contrasting with its pro-apoptotic role on Th1 cells and demonstrating cell-type-specific signaling outcomes.

    Evidence NK92 overexpression, primary NK blocking antibody experiments, Western blotting for ERK and IκBα

    PMID:22323453

    Open questions at the time
    • Molecular basis for opposing outcomes in T cells versus NK cells not explained
    • Adaptor proteins downstream of Tim-3 in NK cells not identified
  9. 2015 High

    Two discoveries expanded galectin-9's functional repertoire: an autocrine TIM-3/Gal-9 loop co-activating NF-κB and β-catenin for AML LSC self-renewal, and an intracellular role as a lysosomal inhibitor that blocks autophagosome–lysosome fusion to selectively kill KRAS-mutant CRC cells.

    Evidence AML xenograft models with neutralizing antibody, NF-κB/β-catenin pathway analysis; confocal endosomal/lysosomal trafficking, autophagy flux assays in isogenic KRAS/BRAF panels

    PMID:26086204 PMID:26279267

    Open questions at the time
    • Direct lysosomal target of galectin-9 not identified
    • Whether intracellular Gal-9 and secreted Gal-9 have distinct structural states not known
    • Mechanism by which KRAS dependency confers selective sensitivity not fully resolved
  10. 2017 High

    Galectin-9 was identified as an endogenous ligand for the innate receptor Dectin-1 on macrophages, revealing a Tim-3-independent immunosuppressive axis in pancreatic cancer where Dectin-1 ligation drives tolerogenic macrophage polarization.

    Evidence Ligand-receptor binding assays, Clec7a-knockout mice, macrophage polarization and T-cell rescue experiments in PDA models

    PMID:28394331

    Open questions at the time
    • Glycan determinants distinguishing Gal-9 binding to Dectin-1 versus Tim-3 not mapped
    • Whether Dectin-1/Gal-9 signaling operates in non-pancreatic tumors not tested
  11. 2021 High

    Discovery that galectin-9 directly binds PD-1 and that PD-1 co-engagement attenuates Tim-3-mediated T-cell death fundamentally reframed the checkpoint: Gal-9 is a multi-receptor hub where PD-1 acts as a protective co-receptor sustaining exhausted T cells.

    Evidence Co-IP and direct binding assays, PD-1-deficient T-cell death comparisons, IFN-β/γ induction experiments, anti-Gal-9 tumor therapy

    PMID:33547304

    Open questions at the time
    • Whether PD-L1 and Gal-9 compete for PD-1 binding not determined
    • Crystal structure of PD-1/Gal-9 complex not available
    • Therapeutic implications of dual PD-1 + Gal-9 blockade versus single blockade not fully characterized
  12. 2021 Medium

    Transcriptional regulation of LGALS9 was delineated: HAND2 activates and FOXO1 represses the LGALS9 promoter in endometrial stromal cells, with FOXO1 phosphorylation relieving suppression; separately, histone H3K9/H3K14 acetylation at the promoter controls expression in cervical cancer cells.

    Evidence Luciferase reporter assays, HAND2/FOXO1 overexpression/knockdown, ChIP for H3K9ac/H3K14ac, bisulfite sequencing

    PMID:32902187 PMID:34581822

    Open questions at the time
    • Whether HAND2/FOXO1 regulation operates outside endometrial tissue not tested
    • Identity of histone acetyltransferases/deacetylases acting at the LGALS9 promoter not determined
  13. 2025 Medium

    Recent studies extended galectin-9's receptor repertoire to CEACAM1 on macrophages (increasing DUSP1 and inhibiting p38 to suppress inflammation) and identified additional signaling contexts including JNK/ERK activation in osteoarthritis chondrocytes and a CD47–HCK–LGALS9 feedback loop in endometrial cancer.

    Evidence Co-IP for CEACAM1–LGALS9, endotoxemia mouse model; RNAi/lentiviral knockdown in OA models; scRNA-seq, organoid–macrophage co-culture, CUT&Tag in endometrial cancer

    PMID:39278441 PMID:40708539 PMID:41437376

    Open questions at the time
    • Direct biochemical binding of galectin-9 to CEACAM1 versus indirect association not fully distinguished
    • Relative contributions of multiple galectin-9 receptors in any single disease context not integrated
    • Whether CD47 is a direct galectin-9 receptor or signals indirectly not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of galectin-9's selective engagement with its expanding receptor repertoire (TIM-3, PD-1, Dectin-1, PDI, CEACAM1), the molecular identity of its intracellular lysosomal target mediating autophagy blockade, and the determinants that switch TIM-3/Gal-9 signaling between pro-apoptotic (T cells) and pro-survival (AML LSCs, NK cells) outcomes.
  • No co-crystal structure for any galectin-9/receptor complex
  • Intracellular lysosomal target not identified
  • Cell-type-specific adaptor proteins downstream of TIM-3 not mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 4 GO:0098631 cell adhesion mediator activity 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005576 extracellular region 4 GO:0031410 cytoplasmic vesicle 3 GO:0005829 cytosol 2 GO:0005764 lysosome 1
Pathway
R-HSA-168256 Immune System 7 R-HSA-162582 Signal Transduction 4 R-HSA-5357801 Programmed Cell Death 3 R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-9612973 Autophagy 2
Partners
CD44CEACAM1CLEC7AHAVCR2P4HBPDCD1PRDX2

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 Galectin-9 (LGALS9) was identified as the ligand for the Tim-3 (TIM-3) receptor on Th1 cells. Galectin-9 binding to Tim-3 induced intracellular calcium flux, cell aggregation, and apoptotic death of Th1 cells in a Tim-3-dependent manner in vitro; in vivo administration selectively depleted IFN-γ-producing cells and suppressed Th1-mediated autoimmunity. In vitro binding assays, calcium flux measurements, cell death assays with Tim-3-deficient cells; in vivo administration in autoimmune models Nature immunology High 16286920
1997 LGALS9 encodes a novel 36-kDa tandem-repeat galectin (galectin-9) with two carbohydrate recognition domains (CRDs) linked by a ~30 amino acid peptide; the protein binds galactosides via affinity chromatography on lactose/galactose resin and is expressed primarily in peripheral blood leukocytes and lymphatic tissues. cDNA cloning, sequence analysis, recombinant protein expression in CHO cells, lactose/galactose affinity chromatography The Journal of biological chemistry High 9045665
1998 A splice variant of LGALS9 (ecalectin) was identified as a T-cell-derived eosinophil chemoattractant. Recombinant ecalectin attracted eosinophils in vitro and in vivo in a dose-dependent manner but not neutrophils, lymphocytes, or monocytes, and is secreted despite lacking a hydrophobic signal peptide. cDNA isolation from T-cell expression library, recombinant protein expression in COS and insect cells, in vitro and in vivo eosinophil chemotaxis assays The Journal of biological chemistry High 9642261
2003 Galectin-9 induces apoptosis via the calcium-calpain-caspase-1 pathway. Gal-9-induced apoptosis of T-cell lines requires beta-galactoside binding (blocked by lactose but not sucrose), induces intracellular Ca2+ influx, and is suppressed by a pan-caspase inhibitor, a caspase-1 inhibitor (Z-YVAD-FMK), a calpain inhibitor (Z-LLY-FMK), the Ca2+ chelator BAPTA-AM, or an IP3 inhibitor; caspase-8, -9, and -10 inhibitors had no effect. Cell death assays with pharmacological inhibitors (caspase, calpain, calcium), calcium flux measurements, lactose competition Journal of immunology High 12646627
2006 EBV-infected NPC cells release exosomes containing galectin-9 (LGALS9); exosomal galectin-9 retains Tim-3-binding capacity and has T-cell inhibitory activity, providing a mechanism for immune escape. Differential centrifugation, immunomagnetic bead purification, Western blotting, T-cell proliferation inhibition assays with anti-Tim-3 and anti-galectin-9 blocking antibodies BMC cancer Medium 17156439
2008 Galectin-9-containing exosomes released by EBV-infected NPC cells circulate in patient plasma, are protected from proteolytic cleavage when encapsulated, retain Tim-3-binding capacity, and induce apoptosis in EBV-specific CD4+ T cells; this effect is blocked by anti-Tim-3 and anti-galectin-9 antibodies. Exosome isolation from patient plasma and xenograft mouse plasma, T-cell apoptosis assays, antibody blockade experiments Blood High 19005181
2010 The Tim-3/galectin-9 signaling pathway promotes expansion of CD11b+Ly-6G+ granulocytic myeloid-derived suppressor cells (MDSCs) to suppress Th1 immunity. Transgenic overexpression of Tim-3 on T cells or overexpression of galectin-9 both increase MDSCs; loss of Tim-3 restores normal MDSC levels in Gal-9 transgenic mice, establishing genetic epistasis in this pathway. Transgenic mouse models (Tim-3 OE, Gal-9 OE), Tim-3 knockout cross, flow cytometry, tumor growth assays Journal of immunology High 20574007
2011 Galectin-9 binds cell surface protein disulfide isomerase (PDI) on Th2 cells, increasing PDI retention on the plasma membrane and altering the redox environment at the cell surface; this galectin-9/PDI interaction enhances T-cell migration through extracellular matrix via β3 integrins and potentiates HIV infection of T cells. Cell surface binding assays, PDI retention measurements, T-cell migration assays, HIV infection assays; galectin-PDI interaction characterized on Th2 vs. Th1 cells Proceedings of the National Academy of Sciences of the United States of America High 21670307
2012 Tim-3 functions as an inducible human NK-cell co-receptor for galectin-9 (LGALS9) that enhances IFN-γ production. Tim-3 overexpression in NK92 cells markedly increased IFN-γ in response to soluble Gal-9 or Gal-9-expressing tumor cells; Tim-3 cross-linking activated ERK and caused IκBα degradation; Tim-3 blockade significantly decreased IFN-γ production. NK cell line overexpression, primary NK cell assays with blocking antibodies, Tim-3 cross-linking, Western blotting (ERK, IκBα), IFN-γ ELISA Blood High 22323453
2012 In HBV-associated hepatocellular carcinoma (HCC), galectin-9 is expressed at highest levels on Kupffer cells in tumor islets; IFN-γ from tumor-infiltrating T cells stimulates galectin-9 expression on antigen-presenting cells; the Tim-3/galectin-9 pathway drives T-cell replicative senescence; blockade of this pathway restores T-cell proliferation and effector cytokine production. Immunofluorescence, flow cytometry, IFN-γ stimulation assays, Tim-3/galectin-9 pathway blockade with antibodies, T-cell functional assays Hepatology High 22505239
2013 Endothelial cells express five LGALS9 splice variants (including two novel ones), with splicing confined to exons 5, 6, and 10. The dominant variant galectin-9Δ5, when overexpressed intracellularly, slightly increased endothelial proliferation; recombinant galectin-9Δ5 dose-dependently inhibited endothelial proliferation and migration and had a small inhibitory effect on angiogenesis in vivo. RT-PCR splice variant identification, HMEC transfection, recombinant protein treatment, proliferation and migration assays, in vivo angiogenesis model Biochimica et biophysica acta Medium 24333696
2013 LGALS9 D5 isoform (galectin-9Δ5) expressed in mouse and human decidua suppresses IFN-γ production by decidual natural killer cells; Lgals9 splice variant expression is differentially regulated during gestation; decreased Lgals9 D5/10 expression is associated with spontaneous abortion. Real-time PCR, immunohistochemistry, mouse gestation model, decidual NK cell functional assays Biology of reproduction Medium 23242525
2015 Recombinant LGALS9 (rLGALS9) is selectively cytotoxic to KRAS-mutant colorectal cancer cells. Upon treatment, rLGALS9 internalizes via early and late endosomes, accumulates in lysosomes, and acts as a lysosomal inhibitor blocking autophagosome-lysosome fusion, leading to autophagosome accumulation, lysosomal swelling, and cell death ('frustrated autophagy'). This activity depends on elevated basal autophagic flux in KRAS-mutant cells and does not occur in BRAF-mutant CRC. Confocal microscopy (endosomal/lysosomal trafficking), autophagy flux assays, cell death assays in isogenic KRAS/BRAF mutant panels, recombinant protein treatment Autophagy Medium 26086204
2015 TIM-3 and galectin-9 (LGALS9) form an autocrine stimulatory loop in human acute myeloid leukemia stem cells (LSCs). TIM-3 is expressed on LSCs but not normal HSCs; Gal-9/TIM-3 signaling co-activates NF-κB and β-catenin pathways to drive LSC self-renewal; neutralization of Gal-9 inhibited xenogeneic reconstitution of human AML in mice. Flow cytometry, AML xenograft models, neutralizing antibody experiments, NF-κB and β-catenin pathway analysis, serum Gal-9 ELISA Cell stem cell High 26279267
2017 Galectin-9 (LGALS9) is an endogenous ligand for the innate immune receptor Dectin-1 on macrophages in pancreatic ductal adenocarcinoma (PDA). Dectin-1 ligation by galectin-9 drives tolerogenic macrophage programming and adaptive immune suppression; deletion of Clec7a (Dectin-1) or blockade of its downstream signaling was protective against PDA progression. Ligand-receptor binding assays (mouse and human PDA), Clec7a-knockout mouse models, macrophage polarization assays, CD4+/CD8+ T-cell functional rescue experiments Nature medicine High 28394331
2017 In AML cells, latrophilin-1 activation drives a PKC- and mTOR-dependent pathway that increases translation and exocytosis of both TIM-3 and galectin-9. TIM-3 participates in galectin-9 secretion and is also released as soluble TIM-3; soluble TIM-3 prevents IL-2 secretion; galectin-9 impairs NK-cell anti-cancer activity. Latrophilin-1 activation, pharmacological inhibition of PKC/mTOR, Western blotting, ELISA, ex vivo validation with primary AML patient samples EBioMedicine Medium 28750861
2020 GBM-derived exosomal LGALS9 in cerebrospinal fluid binds TIM-3 on dendritic cells, inhibiting antigen recognition, processing, and presentation, thereby suppressing cytotoxic T-cell-mediated antitumor immunity; blocking exosomal LGALS9 secretion restored durable DC tumor-antigen-presenting activity and antitumor immunity in mice. CSF exosome proteomics, DC functional assays, TIM-3 binding assays, exosomal LGALS9 knockdown in vivo mouse model, T-cell cytotoxicity assays Cell death & disease Medium 33093453
2021 Galectin-9 (LGALS9) interacts directly with PD-1 in addition to TIM-3. PD-1 binding to galectin-9 attenuates Gal-9/TIM-3-induced T-cell death, thereby promoting persistence of PD-1+TIM-3+ exhausted T cells. Gal-9 expression and secretion are induced by IFN-β and IFN-γ. Co-IP and direct binding assays (PD-1 and galectin-9), T-cell death assays with PD-1-expressing and PD-1-deficient cells, IFN stimulation experiments, anti-Gal-9 therapy in tumor models Nature communications High 33547304
2021 Lgals9 deficiency in mice protected against diet-induced obesity, associated with reduced epididymal and mesenteric fat and improved glucose tolerance. Bone marrow transplant experiments demonstrated the effect is non-hematopoietic cell-intrinsic. Gal-9 physically binds peroxiredoxin-2 (PRDX2) in a sugar-chain-independent manner; Gal-9 knockdown in 3T3-L1 adipocytes shifts PRDX2 from its oxidized dimer to reduced monomer form under H2O2-induced oxidative stress. Lgals9 knockout mice, HFHS diet model, bone marrow transplantation, nanoLC-MS/MS, co-immunoprecipitation, pull-down assay, PRDX2 redox state analysis Scientific reports Medium 33727589
2021 LGALS9 transcription in human endometrial stromal cells is upregulated by the transcription factor HAND2 and downregulated by FOXO1. Phosphorylation of FOXO1 prevents its DNA binding and thus relieves FOXO1-mediated suppression of LGALS9 transcription; steroid hormones regulate LGALS9 expression through modulation of HAND2 expression and FOXO1 phosphorylation status. Luciferase reporter assays for LGALS9 promoter activity, HAND2/FOXO1 overexpression and knockdown, steroid hormone treatment, RT-qPCR, FOXO1 phosphorylation analysis Molecular human reproduction Medium 34581822
2020 Histone H3K9 and H3K14 acetylation at the LGALS9 promoter correlates with and regulates LGALS9 mRNA levels in cervical cancer cells; CpG methylation of the LGALS9 promoter does not explain differences in expression between tumoral and non-tumoral cells. Chromatin immunoprecipitation (ChIP) for H3K9ac and H3K14ac, bisulfite sequencing for CpG methylation, RT-PCR for splice variant identification FEBS open bio Medium 32902187
2024 LGALS9 promotes inflammation in osteoarthritis by activating JNK and ERK1/2 signaling pathways in chondrocytes; LGALS9 knockdown (RNAi and lentivirus) attenuated inflammatory responses in vitro and in vivo OA models. RNAi knockdown, lentiviral overexpression/knockdown, in vitro and in vivo OA models, qRT-PCR, Western blotting for p-JNK and p-ERK1/2, immunofluorescence, safranin staining International journal of biological macromolecules Medium 39278441
2025 Macrophage-derived LGALS9 interacts with the receptor P4HB (beta-subunit of prolyl 4-hydroxylase) on gastric cancer epithelial cells, activating P4HB to enhance tumor cell proliferation, epithelial-mesenchymal transition, and lipid metabolism; pharmacological P4HB inhibition reversed these effects. Single-cell RNA sequencing, ligand-receptor interaction analysis, functional proliferation and EMT assays, pharmacological inhibition of P4HB Journal of cellular and molecular medicine Low 40534096
2025 In early-stage endometrial cancer, tumor cell CD47 stimulates macrophage HCK kinase, driving macrophage secretion of LGALS9, IL-10, and TGF-β1; macrophage-derived LGALS9 in turn signals back through CD47 on tumor cells to reinforce proliferation, establishing a CD47–HCK–LGALS9 positive feedback loop. ERRγ was identified as an upstream transcriptional regulator of CD47 suppressed by progesterone. scRNA-seq, spatial transcriptomics, multiplex immunofluorescence, CCK-8/flow cytometry proliferation assays, GST pull-down mass spectrometry, CUT&Tag, organoid-macrophage co-culture, CD47 inhibition/overexpression Molecular cancer Medium 41437376
2025 Recombinant Lgals9 promotes macrophage polarization toward the M2b phenotype in a cardiac transplant context at appropriate concentrations, as validated by flow cytometry and ELISA. Single-cell RNA sequencing, RT-qPCR, Western blotting, flow cytometry, ELISA, recombinant Lgals9 treatment of macrophages in vitro Journal of leukocyte biology Low 39835675
2025 Intratumoral cell-associated (non-secreted) LGALS9 suppresses cytotoxic T lymphocyte activation in nasopharyngeal carcinoma via a macroautophagy-dependent mechanism. LGALS9 overexpression in NPC cell lines, autophagy manipulation, CTL activation assays (commentary/brief report citing Kam et al. experimental data) Autophagy Low 40698512
2025 Rhamnose binds to CEACAM1 at sites V39, D40, and T101, promoting CEACAM1–LGALS9 interaction in macrophages, which increases DUSP1 protein levels, inhibits p38 phosphorylation, and attenuates LPS-induced proinflammatory cytokine expression. LPS-induced endotoxic mouse model, molecular docking, in vitro macrophage binding assays, CEACAM1-LGALS9 co-immunoprecipitation, Western blotting for DUSP1 and p-p38, cytokine ELISA Acta biochimica et biophysica Sinica Medium 40708539
2025 In keratoconus, LGALS9-positive corneal epithelial cells interact with COMP-positive and CD44-positive stromal cells through LGALS9-CD44 and thrombospondin signaling pathways, promoting extracellular matrix remodeling and a pro-fibrotic/pro-inflammatory network; LGALS9 upregulation in keratoconus corneal epithelium was validated by immunofluorescence and Western blot. Single-cell RNA sequencing, intercellular communication analysis, immunofluorescence, Western blotting in patient keratoconus vs. control corneal tissue International journal of biological macromolecules Low 41022233

Source papers

Stage 0 corpus · 56 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 3725 23128233
2005 The Tim-3 ligand galectin-9 negatively regulates T helper type 1 immunity. Nature immunology 1663 16286920
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2007 Large-scale mapping of human protein-protein interactions by mass spectrometry. Molecular systems biology 733 17353931
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2021 Galectin-9 interacts with PD-1 and TIM-3 to regulate T cell death and is a target for cancer immunotherapy. Nature communications 509 33547304
1994 Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. Gene 492 8125298
2012 Tim-3/galectin-9 signaling pathway mediates T-cell dysfunction and predicts poor prognosis in patients with hepatitis B virus-associated hepatocellular carcinoma. Hepatology (Baltimore, Md.) 414 22505239
2005 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome research 409 16344560
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
2008 Blood diffusion and Th1-suppressive effects of galectin-9-containing exosomes released by Epstein-Barr virus-infected nasopharyngeal carcinoma cells. Blood 355 19005181
2003 Large-scale identification and characterization of human genes that activate NF-kappaB and MAPK signaling pathways. Oncogene 331 12761501
2012 Tim-3 is an inducible human natural killer cell receptor that enhances interferon gamma production in response to galectin-9. Blood 315 22323453
2017 Dectin 1 activation on macrophages by galectin 9 promotes pancreatic carcinoma and peritumoral immune tolerance. Nature medicine 307 28394331
1998 Human ecalectin, a variant of human galectin-9, is a novel eosinophil chemoattractant produced by T lymphocytes. The Journal of biological chemistry 256 9642261
2003 Galectin-9 induces apoptosis through the calcium-calpain-caspase-1 pathway. Journal of immunology (Baltimore, Md. : 1950) 245 12646627
2010 Tim-3/galectin-9 pathway: regulation of Th1 immunity through promotion of CD11b+Ly-6G+ myeloid cells. Journal of immunology (Baltimore, Md. : 1950) 239 20574007
2015 A TIM-3/Gal-9 Autocrine Stimulatory Loop Drives Self-Renewal of Human Myeloid Leukemia Stem Cells and Leukemic Progression. Cell stem cell 228 26279267
1997 Molecular definition of a novel human galectin which is immunogenic in patients with Hodgkin's disease. The Journal of biological chemistry 210 9045665
2006 Exosomes released by EBV-infected nasopharyngeal carcinoma cells convey the viral latent membrane protein 1 and the immunomodulatory protein galectin 9. BMC cancer 205 17156439
2014 Extracellular matrix signatures of human primary metastatic colon cancers and their metastases to liver. BMC cancer 203 25037231
2011 Galectin-9 binding to cell surface protein disulfide isomerase regulates the redox environment to enhance T-cell migration and HIV entry. Proceedings of the National Academy of Sciences of the United States of America 201 21670307
2017 The Tim-3-galectin-9 Secretory Pathway is Involved in the Immune Escape of Human Acute Myeloid Leukemia Cells. EBioMedicine 195 28750861
2018 Role of Galectins in Tumors and in Clinical Immunotherapy. International journal of molecular sciences 179 29389859
2020 TASL is the SLC15A4-associated adaptor for IRF5 activation by TLR7-9. Nature 176 32433612
2022 A new emerging target in cancer immunotherapy: Galectin-9 (LGALS9). Genes & diseases 116 37554219
2020 Exosomal LGALS9 in the cerebrospinal fluid of glioblastoma patients suppressed dendritic cell antigen presentation and cytotoxic T-cell immunity. Cell death & disease 94 33093453
2019 Molecular and immune correlates of TIM-3 (HAVCR2) and galectin 9 (LGALS9) mRNA expression and DNA methylation in melanoma. Clinical epigenetics 59 31747929
2013 Endothelial LGALS9 splice variant expression in endothelial cell biology and angiogenesis. Biochimica et biophysica acta 54 24333696
2015 The epithelial polarity regulator LGALS9/galectin-9 induces fatal frustrated autophagy in KRAS mutant colon carcinoma that depends on elevated basal autophagic flux. Autophagy 42 26086204
2013 Profiling Lgals9 splice variant expression at the fetal-maternal interface: implications in normal and pathological human pregnancy. Biology of reproduction 37 23242525
2018 Role of Lgals9 Deficiency in Attenuating Nephritis and Arthritis in BALB/c Mice in a Pristane-Induced Lupus Model. Arthritis & rheumatology (Hoboken, N.J.) 26 29481735
2020 Histone H3K9 and H3K14 acetylation at the promoter of the LGALS9 gene is associated with mRNA levels in cervical cancer cells. FEBS open bio 18 32902187
2019 Galectin-9 gene (LGALS9) polymorphisms are associated with rheumatoid arthritis in Brazilian patients. PloS one 12 31600237
2021 Gene polymorphisms of LGALS2, LGALS3 and LGALS9 in patients with rheumatoid arthritis. Cellular immunology 9 34371260
2021 Transcriptional regulation of LGALS9 by HAND2 and FOXO1 in human endometrial stromal cells in women with regular cycles. Molecular human reproduction 8 34581822
2015 Variants in the LGALS9 Gene Are Associated With Development of Liver Disease in Heavy Consumers of Alcohol. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association 8 26598225
2024 Summary data-based Mendelian randomization and single-cell RNA sequencing analyses identify immune associations with low-level LGALS9 in sepsis. Journal of cellular and molecular medicine 6 39044269
2024 Potential Plasma Proteins (LGALS9, LAMP3, PRSS8 and AGRN) as Predictors of Hospitalisation Risk in COVID-19 Patients. Biomolecules 4 39334929
2021 Lgals9 deficiency ameliorates obesity by modulating redox state of PRDX2. Scientific reports 4 33727589
2025 Targeting the CD47-HCK-LGALS9 axis disrupts proliferation-immunosuppression coupling in early-stage endometrial cancer. Molecular cancer 2 41437376
2024 Circulating CD8 + LGALS9 + T Cell Population Exhibiting Low Cytotoxic Characteristics are Decreased in Patients with Systemic Lupus Erythematosus. Immunologic research 2 39046608
2024 Study on pro-inflammatory effect and mechanism of galectin-9 (LGALS9) in osteoarthritis: Exacerbating inflammatory response by activating JNK and ERK1/2 pathways. International journal of biological macromolecules 2 39278441
2023 Nicotine Potentially Alters Endothelial Inflammation and Cell Adhesion via LGALS9. Journal of cardiovascular development and disease 2 38248876
2025 Single-cell RNA sequencing revealed the immunophenotypic features of macrophages in cardiac transplants and uncovered Lgals9 promoted their polarization toward the M2b subtype. Journal of leukocyte biology 1 39835675
2025 Myeloid-Derived LGALS9-P4HB Immune Interaction Promotes Metastasis in Gastric Cancer Through Enhanced Cell Proliferation and Lipid Metabolism. Journal of cellular and molecular medicine 1 40534096
2025 Autophagy inhibition in LGALS9-overexpressing nasopharyngeal carcinoma unleashes immune response. Autophagy 0 40698512
2025 Rhamnose alleviates the proinflammatory response during endotoxemia via the CEACAM1/LGALS9-p38 axis. Acta biochimica et biophysica Sinica 0 40708539
2025 Single-cell RNA sequencing reveals LGALS9+ epithelial and COMP+ stromal cell crosstalk driving keratoconus pathogenesis. International journal of biological macromolecules 0 41022233
2025 The LGALS9/miR-491-5p Axis Regulates CD8+ T Cell Function and Inhibits the Progression of Gastric Cancer. Cancer science 0 41171621
2025 MFSD12 promotes proliferation, metastasis and invasion of hepatocellular carcinoma cells and its potential correlation with HAVCR2/LGALS9 immune checkpoint axis. Frontiers in immunology 0 41194934