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主动脉树突状细胞激活T细胞,引发动脉粥样硬化中的局部适应性免疫,加速疾病进展。

Local adaptive immunity in atherosclerosis with T cell activation by aortic dendritic cells accelerates pathogenesis.

作者信息

Zhang Wenjie, Cai Zecheng, Ma Dan, Liu Meng, Wang Juncheng, Sun Li, Lew Andrew M, Xu Yuekang

机构信息

Anhui Provincial Key Laboratory for Conservation and Exploitation of Biological Resources, College of Life Sciences, Anhui Normal University, Wuhu 241000, China.

The Walter and Eliza Hall Institute of Medical Research, University of Melbourne, Parkville, VIC, Australia.

出版信息

iScience. 2024 Oct 10;27(11):111144. doi: 10.1016/j.isci.2024.111144. eCollection 2024 Nov 15.

Abstract

Atherosclerosis represents a chronic inflammatory condition in arterial walls, where local immune cells significantly contribute to disease progression. This study employed various immunological techniques to investigate the specific roles of aortic dendritic cell (DC) subsets in atherosclerotic animal models, distinguishing between normal and diseased immune contexts. Our findings revealed that aortic DCs, particularly the cDC1 subset, played a critical role in facilitating CD8 T cell activation through antigen presentation. Additionally, atherosclerosis-induced increases in GM-CSF levels enhanced CCR7 expression on aortic monocyte-derived DCs, promoting their recruitment and IL-12 production for Th1 differentiation. Notably, immunizing pre-atherosclerotic mice with DC-presented antigens or transferring aortic DCs from atherosclerotic mice resulted in accelerated disease onset. This research elucidates the adaptive immune functions of aortic DCs, offering insights into the cellular mechanisms driving aortic inflammation and potential therapeutic targets for atherosclerosis management.

摘要

动脉粥样硬化是一种动脉壁的慢性炎症性疾病,局部免疫细胞在疾病进展中起重要作用。本研究采用多种免疫学技术,在正常和患病免疫背景下,研究主动脉树突状细胞(DC)亚群在动脉粥样硬化动物模型中的具体作用。我们的研究结果表明,主动脉DC,特别是cDC1亚群,通过抗原呈递在促进CD8 T细胞活化中起关键作用。此外,动脉粥样硬化诱导的GM-CSF水平升高增强了主动脉单核细胞衍生DC上的CCR7表达,促进了它们的募集和IL-12的产生以促进Th1分化。值得注意的是,用DC呈递的抗原免疫动脉粥样硬化前期小鼠或转移来自动脉粥样硬化小鼠的主动脉DC会导致疾病发作加速。这项研究阐明了主动脉DC的适应性免疫功能,为驱动主动脉炎症的细胞机制以及动脉粥样硬化管理的潜在治疗靶点提供了见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e42/11536043/96ad78847683/fx1.jpg

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