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

- The IL-22 receptor is expressed in the vascular wall.
- IL-22−/−Apoe−/− mice develop reduced plaque size.
- IL-22 stimulates down regulation of contractile smooth muscle cell genes.

ObjectiveIL-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.MethodsWe generated IL-22−/−Apoe−/− mice and fed them high-fat-diet for 14 weeks to characterize atherosclerosis development.ResultsIL-22−/−Apoe−/− mice exhibited reduced plaque size both in the aorta (p = 0.0036) and the aortic root compared (p = 0.0012) with Apoe−/− controls. Moreover, plaque collagen was reduced in IL-22−/−Apoe−/− mice (p = 0.02) and this was associated with an increased expression of smooth muscle cell (SMC)-α-actin (p = 0.04) and caldesmon (p = 0.016) in the underlying media. Carotid arteries from IL-22−/−Apoe−/− mice displayed increased expression of genes associated with a contractile SMC phenotype e.g. α-actin (p = 0.004) and caldesmon (p = 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.ConclusionOur observations demonstrate that IL-22 is involved in plaque formation and suggest that IL-22 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.