Apolipoprotein E derived from CD11c+ cells ameliorates atherosclerosis

• Published in: iScience Vol. 25; no. 1; p. 103677
• Main Authors: Sauter, Manuela, Sauter, Reinhard J., Nording, Henry, Lin, Chaolan, Olbrich, Marcus, Autenrieth, Stella, Gleissner, Christian, Thunemann, Martin, Otero, Nadia, Lutgens, Esther, Aherrahrou, Zouhair, Wolf, Dennis, Zender, Lars, Meuth, Sven, Feil, Robert, Langer, Harald F.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 21.01.2022; Elsevier
• Subjects: Biological sciences; Components of the immune system; Immune response; Molecular biology; Biological sciences; Immune response; Molecular biology; Components of the immune system
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2021.103677

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. [Display omitted] •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 atherosclerosis Biological sciences; Molecular biology; Immune response; Components of the immune system