Open AccessInterleukin‐13 protects from atherosclerosis and modulates plaque composition by skewing the macrophage phenotype
Author(s) -
CardiloReis Larissa,
Gruber Sabrina,
Schreier Sabine M.,
Drechsler Maik,
PapacMilicevic Nikolina,
Weber Christian,
Wagner Oswald,
Stangl Herbert,
Soehnlein Oliver,
Binder Christoph J.
Publication year - 2012
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.1002/emmm.201201374
Subject(s) - macrophage , cytokine , monocyte , foam cell , chemistry , interleukin , infiltration (hvac) , interleukin 4 , phenotype , immunology , microbiology and biotechnology , in vitro , biology , biochemistry , materials science , composite material , gene
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.