deficiency accelerates unstable atherosclerotic plaque formation in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol 2012;32:273–280

Objective—Interleukin(IL)-17A, an inflammatory cytokine, has been implicated in atherosclerosis, in which inflammatory cells within atherosclerotic plaques express IL-17A. However, its role in the development of atheroscelrosis remains to be controversial. Methods and Results—To directly examine the role of IL-17A in atherosclerosis, we generated apolipoprotein E (ApoE)/IL-17A double-deficient (ApoE/IL-17A/) mice. Mice were fed with high-fat diet (HFD) for either 8 or 16 weeks, both starting at ages of 6 to 8 weeks. We found that splenic CD4 T-cells produced high amounts of IL-17A in ApoE/ mice after HFD feeding for 8 weeks. Atherosclerosis was significantly accelerated in HFD-fed ApoE/IL-17A/ mice compared with ApoE/ mice. Splenic CD4 T-cells of ApoE/IL-17A/ mice after HFD feeding for 8 weeks, but not for 16 weeks, exhibited increased interferon gamma and decreased IL-5 production. Importantly, formation of vulnerable plaque as evidenced by reduced numbers of vascular smooth muscle cells and reduced type I collagen deposition in the plaque was detected in ApoE/IL-17A/ mice after HFD feeding for 8 weeks. Conclusion—These results suggest that IL-17A regulates the early phase of atherosclerosis development after HFD feeding and plaque stability, at least partly if not all by modulating interferon gamma and IL-5 production from CD4 T-cells. (Arterioscler Thromb Vasc Biol. 2012;32:273-280.