摘要：SummaryAtherosclerosis 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 CD11ccre+ApoEfl/fland Albumincre+ApoEfl/flmice, 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.Graphical abstractDisplay OmittedHighlights•CD11c+cells are enriched in aortae of high cholesterol-fed ApoE−/-mice•Depletion of CD11c+cells increases plaque size in ApoE−/-mice•≈ 20% of serum ApoE derives from CD11c+cells•ApoE from CD11c+cells contributes to protection from atherosclerosisBiological sciences; Molecular biology; Immune response; Components of the immune system
