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

动脉粥样硬化局部适应性免疫,主动脉树突状细胞激活 T 细胞加速发病机制

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

Abstract

Atherosclerosis represents a chronic inflammatory condition in arterial walls, where local immune cells significantly contribute to disease progression. This study employed various in situ 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.

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