Interleukin-17-Producing CD4+ T Cells Promote Inflammatory Response and Foster Disease Progression in Hyperlipidemic Patients and Atherosclerotic Mice

作者：Yin Wang, Wenming Li, Tingrui Zhao, Yao Zou, Tao Deng, Zhangyou Yang, Zhiyi Yuan, Limei Ma, Ruihong Yu, Tingting Wang, Chao Yu · 发表于：Frontiers in Cardiovascular Medicine · 年份：2021 · DOI：10.3389/fcvm.2021.667768 · 被引用次数：31 · 研究领域：Atherosclerosis and Cardiovascular Diseases、Psoriasis: Treatment and Pathogenesis、T-cell and B-cell Immunology

Atherosclerosis is a chronic inflammatory disease. Interleukin-17-producing CD4 + T cells (Th17 cells) play important roles in the progression of atherosclerosis. However, most of the studies were focused on the advanced stage of atherosclerosis. In the current study, we investigated the roles of Th17 cells, relevant mechanisms in hyperlipidemic patients, and different stages of atherosclerotic mice. Human blood samples were collected, and percentages of Th17 cells, macrophages, and neutrophils were analyzed by flow cytometry. ApoE −/− mice were fed with high-fat diet (HFD) and sacrificed at different time points to evaluate the infiltration of inflammatory cells at different stages of atherosclerosis. Furthermore, essential mechanisms of IL-17A in atherosclerotic inflammatory milieu formation were studied in vivo by intraperitoneal injection with monoclonal anti-murine IL-17 antibody. Our study reveals the higher percentages of Th17 cells, monocytes, and neutrophils in hyperlipidemic patients compared to healthy donors. Meanwhile, we also identify an infiltration of Th17 cells in the early stage of atherosclerosis (4 weeks after HFD), which maintains at high level until late stage of atherosclerosis (20 weeks after HFD). What is more, inflammatory cells including macrophages and neutrophils were also accumulated in atherosclerotic lesions. Neutralization of IL-17 in ApoE −/− mice resulted in less infiltration of macrophages and neutrophils and smaller atherosclerotic lesions...