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Tissue factor-dependent colitogenic CD4+ T cell thrombogenicity is regulated by activated protein C signalling

Author

Listed:
  • Gemma Leon

    (RCSI University of Medicine and Health Sciences)

  • Paula A. Klavina

    (RCSI University of Medicine and Health Sciences)

  • Aisling M. Rehill

    (RCSI University of Medicine and Health Sciences)

  • Sarah E. J. Cooper

    (CHI-Crumlin)

  • Anna Dominik

    (CHI-Crumlin)

  • Shrikanth Chomanahalli Basavarajappa

    (Trinity College Dublin)

  • James S. O’Donnell

    (RCSI University of Medicine and Health Sciences)

  • Seamus Hussey

    (CHI-Crumlin)

  • Patrick T. Walsh

    (Trinity College Dublin)

  • Roger J. S. Preston

    (RCSI University of Medicine and Health Sciences)

Abstract

Patients with inflammatory bowel disease (IBD) have an increased risk of venous thromboembolism (VTE), but the underlying mechanistic basis remains poorly defined. Here, we find that colitogenic CD4+ T cells express tissue factor (TF) and promote rapid TF-dependent plasma thrombin generation. TF+CD3+CD4+ T cells are present in both the colons of mice with experimental colitis and blood and colonic tissue from patients with IBD. Expression of genes involved in regulating coagulation, including Protein C (PC; encoded by PROC) and its receptor (PROCR), are dysregulated in IBD patient gut biopsy tissues. Moreover, activated PC signalling reduces the procoagulant activity mediated by TF+CD4+ T cells. Our data thus identify TF-induced, colitogenic T cell-mediated thrombogenicity, and also demonstrate a new function for activated PC signalling in regulating T cell thrombo-inflammatory activity.

Suggested Citation

  • Gemma Leon & Paula A. Klavina & Aisling M. Rehill & Sarah E. J. Cooper & Anna Dominik & Shrikanth Chomanahalli Basavarajappa & James S. O’Donnell & Seamus Hussey & Patrick T. Walsh & Roger J. S. Prest, 2025. "Tissue factor-dependent colitogenic CD4+ T cell thrombogenicity is regulated by activated protein C signalling," Nature Communications, Nature, vol. 16(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57001-7
    DOI: 10.1038/s41467-025-57001-7
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    References listed on IDEAS

    as
    1. Satish Ranjan & Alexander Goihl & Shrey Kohli & Ihsan Gadi & Mandy Pierau & Khurrum Shahzad & Dheerendra Gupta & Fabian Bock & Hongjie Wang & Haroon Shaikh & Thilo Kähne & Dirk Reinhold & Ute Bank & A, 2017. "Activated protein C protects from GvHD via PAR2/PAR3 signalling in regulatory T-cells," Nature Communications, Nature, vol. 8(1), pages 1-16, December.
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