CD11b+Gr-1+ myeloid-derived suppressor cells reduce atherosclerotic lesion development in LDLr deficient mi
Publication by: Amanda Foks, Gijs van Puijvelde, Jolien Wolbert, Mara Kröner, Vanessa Frodermann, Thomas van der Heijden, Peter van Santbrink, Louis Boon, Ilze Bot and Johan Kuiper. Cardiovascular Research. 2016;111(3):252-261.
Cellular therapy is one of the emerging therapeutic strategies to prevent or inhibit a number of diseases, as this kind of therapy uses the body’s own cells to treat the disease. Also in atherosclerosis, cellular therapy could be beneficial. Foks and co-authors have recently published the paper “CD11b+Gr-1+ myeloid-derived suppressor cells reduce atherosclerotic lesion development in LDLr deficient mice” in Cardiovascular Research, in which the therapeutic potential of myeloid-derived suppressor cells (MDSCs) in treating atherosclerosis was investigated. Myeloid-derived suppressor cells (MDSCs) form a heterogeneous population of cells composed of early myeloid progenitor cells and immature myeloid cells, which strongly suppress pro-inflammatory immune cells in inflammatory diseases. Up to now, it was unknown whether MDSCs contribute to atherosclerosis, a chronic inflammatory disease in which accumulation of lipoproteins in the arterial wall activates the immune system causing abnormal vascular remodelling and vessel occlusion. In this study, we investigated whether and how MDSCs contribute to the development of atherosclerosis.
We showed that MDSCs arise in the bone marrow during atherosclerosis and strongly suppress proliferation of T cells. Adoptive transfer of MDSCs into Western-type diet fed mice inhibited atherosclerosis with 35%. We observed a 54% reduction in adventitial T cells, and more specifically, MDSCs suppressed Th1 and Th17 cells. In addition, treatment with MDSCs reduced circulating pro-atherogenic B2 cells. We found two subsets of MDSCs in the bone marrow: monocytic and granulocytic MDSCs (mo- and gr-MDSCs, respectively), of which the percentage of mo-MDSCs significantly increased during WTD feeding. Moreover, mo-MDSCs completely abolished splenocyte proliferation, whereas gr-MDSCs were unable to suppress proliferation. Mechanistically, we showed that MDSCs suppress T cells in an IFN-γ- and nitric oxide-dependent manner, which is associated with the action of mo-MDSCs.
In conclusion, this study demonstrated that MDSCs develop during atherosclerosis and reduced atherosclerosis via suppression of pro-inflammatory immune responses.
Cardiovascular Research is the international journal of the European Society of Cardiology for basic and translational research, across different disciplines and areas. The Journal aims to enhance insight in cardiovascular disease mechanisms and the perspective for innovation, and has an impact factor of 5.465 (2015).