Apolipoprotein E derived from CD11c(+) cells ameliorates atherosclerosis

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.