{
  "abstract": "Background: Venous thromboembolism is increasingly recognized as a thrombo-inflammatory disease, yet the pathways linking inflammation to venous thrombus initiation remain incompletely defined. Galectin-9 (Gal-9), a {beta}-galactoside-binding lectin elevated in inflammatory disorders, has no defined role in venous thrombosis. Methods: Using plasma from patients with deep vein thrombosis (DVT), Gal-9-deficient mice, an inferior vena cava stenosis model, intravital microscopy, microfluidics, and ex vivo platelet and neutrophil assays, we assessed the functional contribution of Gal-9 to venous thrombosis. Results: Plasma Gal-9 was elevated in DVT patients, correlated with D-dimer at presentation, and declined over 3-month follow-up. Gal-9 deletion did not alter hemostasis but markedly impaired thrombus initiation, with reduced platelet and neutrophil recruitment to the vessel wall and reduced intra-thrombus neutrophil extracellular trap (NET) formation. TNF-/IFN-{gamma}-stimulated endothelial cells upregulated Gal-9 and promoted platelet adhesion and fibrin(ogen) deposition, which Gal-9 neutralization partially reversed. Under venous shear, immobilized recombinant Gal-9 potentiated platelet activation and thrombus formation, particularly alongside collagen, whereas Gal-9 inhibition suppressed these responses. Gal-9-activated platelets promoted NETosis and shifted thrombus composition toward a NET-rich inflammatory phenotype. Conclusions: Gal-9 is a previously unrecognized driver of venous thrombo-inflammation, linking vascular inflammation to platelet activation, NET formation, and thrombosis. Genetic deletion attenuated these responses in vivo, and antibody-mediated Gal-9 neutralization suppressed platelet activation and thrombus formation in vitro, identifying the Gal-9 glycan-binding pathway as a therapeutic target that disrupts thrombosis without impairing hemostasis.",
  "abstract_shown": true,
  "affiliations": [
    "University of Birmingham"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 15,
  "authors": [
    {
      "name": "A. A. Konkoth"
    },
    {
      "name": "A. Abo Mansour"
    },
    {
      "name": "K. Whitworth"
    },
    {
      "name": "I. Budnik"
    },
    {
      "name": "D. Steiner"
    },
    {
      "name": "C. Ay"
    },
    {
      "name": "D. Lezama"
    },
    {
      "name": "H. M. McGettrick"
    },
    {
      "name": "D. Kavanagh"
    },
    {
      "name": "F. Maione"
    },
    {
      "name": "J. El-Awaisi"
    },
    {
      "name": "G. E. Rainger"
    },
    {
      "name": "J. Rayes"
    },
    {
      "name": "A. Brill"
    },
    {
      "affs": [
        0
      ],
      "name": "A. J. Iqbal"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4hezd89znpehm.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.11.05.757779",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.11.05.757779v1.full",
  "id": "4hezd89znpehm",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.11.05.757779v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "immunology"
    ]
  ],
  "openalex": null,
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.11.05.757779v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-05",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/4hezd89znpehm.ris",
  "sources": [
    {
      "first_seen": "2026-11-07T00:21:26Z",
      "native_id": "10.64898/2026.11.05.757779",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.11.05.757779v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:immunology",
      "subfield": "immunology"
    }
  ],
  "title": "Galectin-9 drives thrombo-inflammatory circuits initiating venous thrombosis",
  "title_text": "Galectin-9 drives thrombo-inflammatory circuits initiating venous thrombosis",
  "type": "preprint",
  "updated_at": "2026-11-08T00:21:10Z",
  "url": "https://research.draconitic.com/paper/4hezd89znpehm",
  "venue": "bioRxiv",
  "versions": []
}