Abstract 153: IL-17 Amplifies Thrombosis in a Mouse Model of DVT

Background: Immune cells are known to participate in thrombosis. A subset of IL-17 producing T-cells plays a role in the inflammatory dysregulation of inflammatory bowel disease, malignancy, and acute graft rejection. IL-17 resides at the interface between innate and adaptive immunity, exerting pro-inflammatory effects via induction of cytokines and cellular adhesion molecules, with consequent neutrophil activation and mobilization. Inflammatory properties of endothelium itself direct T-cell plasticity, and we have previously demonstrated that endothelial CD39 is an important inflammatory regulator via degradation of pro-inflammatory nucleotides. It is unknown whether IL-17 affects development of thrombosis in deep veins. Hypothesis: IL-17 released from T-cells augments deep venous thrombosis, through endothelial CD39-driven T-cell phenotype switching. Methods: A uniform non-occluding ligature around the infrarenal IVC was used to model DVT. CD39 haploinsufficient (CD39+/-) mice were used, as full knockouts demonstrate baseline platelet reactivity abnormalities affecting thrombosis. Mice were sacrificed at 48 hours and IVC and thrombus harvested. IL-17 protein was measured using western blotting and immunohistochemistry and inflammatory cells in vein wall were identified by flow cytometry. Results: CD39 +/- mice had increased thrombus mass compared to wild-type animals (p=0.02), with a corresponding increase in IL-17. In CD39 +/- mice, immunohistochemistry of thrombus indicated increased inflammatory cell infiltration, expression of VCAM-1 and IL-17. In vitro confirmation of effect of IL-17 dosing of HUVEC induced a 2-fold induction of E-Selectin (p Conclusion: Decreased expression of CD39 is associated with a pro-thrombotic phenotype in CD39 haploinsufficient mice, resulting in increased IL-17 within the IVC, inducing Selectin- and CAM-driven pathways of inflammatory cell infiltration after thrombosis.