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Apolipoprotein E derived from CD11c+ cells ameliorates atherosclerosis

Sauter, M;Sauter, R;Nording, H;Lin, C;Olbrich, M;Autenrieth, S;Gleissner, C;Thunemann, M;Otero, N;Lutgens, E;Aherrahrou, Z;Wolf, D;Zender, L;Meuth, S;Feil, R;Langer, H;

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 CD11ccre+ApoEfl/fl and Albumincre+ApoEfl/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.