IL-17A promotes the formation of deep vein thrombosis in a mouse model.

Deep venous thrombosis (DVT) is a significant problem in the health care industry worldwide. However, the factors and signaling pathways that trigger DVT formation are still largely unknown. In this study, we investigated the role of interleukin-17A (IL-17A) in DVT formation, focusing on the role of platelet aggregation, neutrophil infiltration, and endothelium cell (EC) activation. Notably, IL-17A levels increased in DVT patients as well as in a mouse DVT model. The DVT model mice were injected with recombinant mouse-IL-17A (rIL-17A) or anti-IL-17A monoclonal antibody (mAb) to further evaluate the effects of this cytokine. We found that rIL-17A promotes DVT formation, while IL-17A mAb represses DVT formation. Furthermore, platelet activation, highlighted by CD61 and CD49β expression, and aggregation were enhanced in platelets of rIL-17A-treated mice. rIL-17A also enhanced neutrophil infiltration by regulating the expression of macrophage inflammatory protein-2 (MIP-2) and the release of neutrophil extracellular traps (NETs). IL-17A mAb treatment inhibited both platelet activation and neutrophil activity. Moreover, rIL-17A appears to promote vein EC activation, while IL-17A mAb deters it. Taken together, these data suggest that IL-17A promotes DVT pathogenesis by enhancing platelet activation and aggregation, neutrophil infiltration, and EC activation and that anti-IL-17A mAb could be used for the treatment of DVT.