IL-22 affects smooth muscle cell phenotype and plaque formation in apolipoprotein E knockout mice

Objective: IL-22 is a recently discovered cytokine that belongs to the family of IL-10 related cytokines. It is produced by activated T-cells and innate lymphoid cells and has been suggested to be involved in tissue repair. As both inflammation and repair play important roles in atherosclerosis we investigated if IL-22 deficiency influences the disease process in Apoe � /� mice. Methods: We generated IL-22 � /� Apoe � /� mice and fed them high-fat-diet for 14 weeks to characterize atherosclerosis development. Results: IL-22 � /� Apoe � /� mice exhibited reduced plaque size both in the aorta (p ¼ 0.0036) and the aortic root compared (p ¼ 0.0012) with Apoe � /� controls. Moreover, plaque collagen was reduced in IL-22 � / � Apoe � /� mice (p ¼ 0.02) and this was associated with an increased expression of smooth muscle cell (SMC)-a-actin (p ¼ 0.04) and caldesmon (p ¼ 0.016) in the underlying media. Carotid arteries from IL22 � /� Apoe � /� mice displayed increased expression of genes associated with a contractile SMC phenotype e.g. a-actin (p ¼ 0.004) and caldesmon (p ¼ 0.03). Arterial SMCs were shown to express the IL-22 receptor and in vitro exposure to IL-22 resulted in a down-regulation of alpha actin and caldesmon gene expression in these cells. Conclusion: Our observations demonstrate that IL-22 is involved in plaque formation and suggest that IL22 released by immune cells is involved in activation of vascular repair by stimulating medial SMC dedifferentiation into a synthetic phenotype. This response contributes to plaque growth by enabling SMC migration into the intima but may also help to stabilize the plaque.