Abstract 543: Regulation of Atherosclerosis by Myeloid-Derived Suppressor Cells
Objective: Restoration of immune homeostasis in atherosclerosis represents the ultimate goal of an immune-based therapy. Myeloid-derived suppressor cells (MDSCs) are a population of immature myeloid cells that potently suppress immune responses in various pathological settings, via multiple mechanisms, including inhibition of T cell responses. They express the myeloid markers CD11b and Gr-1 and can accumulate in various lymphoid and non-lymphoid tissues. In the present study, we determined the role of MDSCs in atherosclerosis by an adoptive transfer of CD11b+Gr-1+ cells into LDLr-/- mice fed a Western-type diet.
Methods and Results: We isolated CD11b+Gr-1+ cells from the bone marrow of LDLr-/- mice fed a Western-type diet for 2 weeks with magnetic beads and found that they strongly suppressed αCD3/CD28-induced splenocyte proliferation in an IFN-γ and iNOS-dependent manner. Subsequently, we adoptively transferred MDSCs into LDLr-/- mice fed a Western-type diet for 6 weeks, which resulted in a 35% reduction in atherosclerotic lesion formation in the aortic root. MDSC treatment reduced splenic Th1 and Th17 cells with 50% and diminished B cells, in particular circulating B2 cells, and concomitantly impaired their proliferative capacity.
Conclusions: Our data prove that MDSCs could represent a novel cell-based immune-therapy to dampen pro-atherogenic immune responses and thereby reduce atherosclerosis.
Author Disclosures: A.C. Foks: None. G.H.M. van Puijvelde: None. V. Frodermann: None. T. van der Heiden: None. I. Bot: None. J. Kuiper: None.
- © 2014 by American Heart Association, Inc.