Tissue factor-dependent colitogenic CD4+ T cell thrombogenicity is regulated by activated protein C signalling
Gemma León, Paula Klavina, Aisling M. Rehill, Sarah E. J. Cooper, Anna Dominik, Shrikanth Chomanahalli Basavarajappa, James S. O’Donnell, Séamus Hussey, Patrick Walsh, Roger J. S. Preston
Abstract
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.