Lack of T-bet reduces monocytic interleukin-12 formation and accelerates thrombus resolution in deep vein thrombosis

The role of leukocytes in deep vein thrombosis (DVT) resolution is incompletely understood. We determined how depletion of lysozyme positive (LysM + ) cells and a switched-off type 1 immune response influences thrombus resolution. DVT was induced in 12-week-old male mice by inferior vena cava (IVC) stenosis. Toxin mediated depletion of myeloid cells improved thrombus resolution in mice with Cre-inducible expression of the diphtheria toxin receptor in LysM + cells. This correlated with decreased CD45 + cells, a population shift of Gr-1 + to Gr-1 − CD11b + myelomonocytic cells (flow cytometry) and an increase in CC-chemokine ligand 2, interleukin-4 and interleukin-10 mRNA expressions. Tbx21 −/− mice (lacking transcription factor T-bet and marked by an attenuated type 1 immune response) with DVT had faster thrombus resolution, a reduction of pro-inflammatory Ly6C hi monocytes in thrombi and decreased interleukin-12p40 mRNA expression than control mice resulting in increased vascular endothelial growth factor mRNA expression and improved neovascularization of thrombotic veins. Transfer of Tbx21 −/− bone marrow into irradiated Tbx21 +/+ recipients lead to accelerated thrombus resolution with lower T-bet-dependent interleukin-12p40 mRNA levels following IVC-stenosis. We conclude that inhibition of Tbet + interleukin-12 forming myelomonocytic cells accelerated thrombus resolution. Modulating the inflammatory immune response might be an approach to improve therapy of DVT.