Interleukin‐13 protects from atherosclerosis and modulates plaque composition by skewing the macrophage phenotype
Open Access
- 2 October 2012
- journal article
- research article
- Published by Springer Science and Business Media LLC in EMBO Molecular Medicine
- Vol. 4 (10), 1072-1086
- https://doi.org/10.1002/emmm.201201374
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.Keywords
This publication has 67 references indexed in Scilit:
- Divergent expression patterns of IL-4 and IL-13 define unique functions in allergic immunityNature Immunology, 2011
- Monocyte trafficking in acute and chronic inflammationTrends in Immunology, 2011
- Caveolin‐1 deficiency decreases atherosclerosis by hampering leukocyte influx into the arterial wall and generating a regulatory T‐cell responseThe FASEB Journal, 2011
- HDL promotes rapid atherosclerosis regression in mice and alters inflammatory properties of plaque monocyte-derived cellsProceedings of the National Academy of Sciences of the United States of America, 2011
- Alternative Activation of Macrophages: Mechanism and FunctionsImmunity, 2010
- Molecular and Structural Basis of Cytokine Receptor Pleiotropy in the Interleukin-4/13 SystemCell, 2008
- Cellular and molecular mechanisms of fibrosisThe Journal of Pathology, 2007
- Monocyte accumulation in mouse atherogenesis is progressive and proportional to extent of diseaseProceedings of the National Academy of Sciences of the United States of America, 2006
- Inflammation, Atherosclerosis, and Coronary Artery DiseaseThe New England Journal of Medicine, 2005
- Innate and acquired immunity in atherogenesisNature Medicine, 2002