Natural killer cells induce neutrophil extracellular trap formation in venous thrombosis

Conclusions: Thrombus formation was reduced in Tbet‐/‐ and IFN γ‐/‐ mice, suggesting that Tbet/IFN γ expressing cells are required for venous thrombosis. The number of NETs formed during thrombosis was significantly lower in Tbet‐/‐ and IFN γ‐/‐ mice. NET formation was also decreased in WT mice treated with an IFN γ blocking antibody. Injection of recombinant IFNγ in IFNγ‐/‐ mice rescued the phenotype. Natural killer (NK) cells were specifically depleted prior to venous thrombosis induction. NK cell depletion results in decreased NET formation and smaller thrombi suggesting that NK cells are required for thrombus development. In depleted mice, adoptive transfer of WT NK cells induced similar thrombosis burden as in WT mice. In contrast, adoptive transfer of IFN γ‐/‐ NK cells results in thrombus similar in size to depleted mice. In vitro, we show that WT neutrophils release fewer NETs when co ‐cultured with IFNγ‐/‐ NK cells. This study demonstrates that NK cell ‐dependent IFNγ production is crucial for thrombus development by promoting the formation of NETs by neutrophils.This article is protected by copyright. All rights reserved.

Source: Journal of Thrombosis and Haemostasis - November 20, 2018 Category: Hematology Authors: Fran çois‐René Bertin, Ryan N. Rys, Cedric Mathieu, Sandrine Laurance, Catherine A. Lemarié, Mark D. Blostein Tags: Original Article ‐ Vascular Biology Source Type: research