Citation

Atherosclerosis is studied in models with dysfunctional lipid homeostasis—predominantly the ApoE^−/− mouse. The role of antigen-presenting cells (APCs) for lipid homeostasis is not clear. Using a LacZ reporter mouse, we showed that CD11c⁺ cells were enriched in aortae of ApoE^−/− mice. Systemic long-term depletion of CD11c⁺ cells in ApoE^−/− mice resulted in significantly increased plaque formation associated with reduced serum ApoE levels. In CD11c^cre+ApoE^fl/fl and Albumin^cre+ApoE^fl/fl mice, we could show that ≈70% of ApoE is liver-derived and ≈25% originates from CD11c⁺ cells associated with significantly increased atherosclerotic plaque burden in both strains. Exposure to acLDL promoted cholesterol efflux from CD11c⁺ cells and cell-specific deletion of ApoE resulted in increased inflammation reflected by increased IL-1β serum levels. Our results determined for the first time the level of ApoE originating from CD11c⁺ cells and demonstrated that CD11c⁺ cells ameliorate atherosclerosis by the secretion of ApoE.