title: Interleukin-13 protects from atherosclerosis and modulates plaque composition by skewing the macrophage phenotype.
abstract: Atherosclerotic lesions are characterized by the accumulation of oxidized LDL (OxLDL) and the infiltration of macrophages and T cells. Cytokine expression in the microenvironment of evolving lesions can profoundly contribute to plaque development. While the pro-atherogenic effect of T helper (Th) 1 cytokines, such as IFN-γ, is well established, the role of Th2 cytokines is less clear. Therefore, we characterized the role of the Th2 cytokine interleukin (IL)-13 in murine atherosclerosis. Here, we report that IL-13 administration favourably modulated the morphology of already established atherosclerotic lesions by increasing lesional collagen content and reducing vascular cell adhesion molecule-1 (VCAM-1)-dependent monocyte recruitment, resulting in decreased plaque macrophage content. This was accompanied by the induction of alternatively activated (M2) macrophages, which exhibited increased clearance of OxLDL compared to IFN-γ-activated (M1) macrophages in vitro. Importantly, deficiency of IL-13 results in accelerated atherosclerosis in LDLR(-/-)  mice without affecting plasma cholesterol levels. Thus, IL-13 protects from atherosclerosis and promotes a favourable plaque morphology, in part through the induction of alternatively activated macrophages.
authors.affiliation: Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.
authors.forename: Larissa
authors.initials: L
authors.lastname: Cardilo-Reis
authors.forename: Sabrina
authors.initials: S
authors.lastname: Gruber
authors.forename: Sabine M
authors.initials: SM
authors.lastname: Schreier
authors.forename: Maik
authors.initials: M
authors.lastname: Drechsler
authors.forename: Nikolina
authors.initials: N
authors.lastname: Papac-Milicevic
authors.forename: Christian
authors.initials: C
authors.lastname: Weber
authors.forename: Oswald
authors.initials: O
authors.lastname: Wagner
authors.forename: Herbert
authors.initials: H
authors.lastname: Stangl
authors.forename: Oliver
authors.initials: O
authors.lastname: Soehnlein
authors.forename: Christoph J
authors.initials: CJ
authors.lastname: Binder
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000473:pathology* / Q000517:prevention & control*; D002784:Cholesterol / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D018793:Interleukin-13 / Q000276:immunology* / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000032:analysis; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice
chemical_list: D018793:Interleukin-13; D008077:Lipoproteins, LDL; D002784:Cholesterol