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

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.