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journal article·2025-06Open access

IRF8 Drives Conventional Type 1 Dendritic Cell Differentiation and CD8 + T Cell Activation to Aggravate Abdominal Aortic Aneurysm Development

Zhen Yuan, Li Shu, Yidan Zheng, Yidong Wang, Mengsha Zheng, Jie Sun, Jiantao Fu, Zihao Zhou, Shen Song, Zhenjie Liu, Fei Li, Zhejun Cai

Advanced Science· Volume 12· Issue 22
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Abstract

Abstract Abdominal aortic aneurysm (AAA) is the most common true aneurysm worldwide, and recent studies suggest that dendritic cells (DCs) play a key role in its development, though the specific subtypes and underlying mechanisms remain unclear. In this study, the role of interferon regulatory factor 8 (IRF8) in AAA is investigated by focusing on its effect on the differentiation of DC precursors into conventional type 1 dendritic cells (cDC1s). It is found significant infiltration of HLA‐DR + IRF8 + cells in human AAA tissue samples. In mice, DC‐specific overexpression of Irf8 exacerbates aneurysm expansion following periadventitial elastase application, while DC‐specific Irf8 deletion attenuates AAA development. Batf3 −/− mice, which lack cDC1s, exhibit AAA characteristics similar to the Irf8 ‐deleted mice. Additionally, an increased population of activated CD8 + T cells is observed in the DC‐ Irf8 overexpressed mice, while the DC‐ Irf8 deletion mice show a decrease in these cells. Blocking antigen cross‐presentation to CD8 + T cells also reduces AAA progression. Tissue microarray analysis of human aortic samples further confirms a correlation between IRF8 expression and AAA development. These findings suggest that IRF8 activation promotes cDC1 differentiation, leading to the recruitment of CD8 + T cells, which contribute to aortic wall destruction and AAA formation.
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Research context

OpenAlex topics: Aortic aneurysm repair treatments · Macrophage Migration Inhibitory Factor · Immune cells in cancer

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Cardiology The Second Affiliated Hospital, School of Medicine Heart Regeneration and Repair Key Laboratory of Zhejiang Province Hangzhou 310009 China

State Key Laboratory of Transvascular Implantation Devices Hangzhou 310009 China

Heart Regeneration and Repair Key Laboratory of Zhejiang Province Hangzhou 310009 China

Transvascular Implantation Devices Research Institute Hangzhou 310053 China

Department of Cardiovascular Surgery Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 China

Department of Pathology The Second Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310009 China

Beijing Anzhen Hospital of Capital Medical University and Beijing Institute of Heart Lung and Blood Vessel Diseases Beijing 100029 China

Clinical Center for HIV/AIDS Beijing Ditan Hospital Capital Medical University Beijing 100015 China

State Key Laboratory of Cardiovascular Disease Fuwai Hospital National Center for Cardiovascular Disease Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100037 China

Department of Vascular Surgery The Second Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310009 China

Department of Structural Heart Disease Fuwai Yunnan Cardiovascular Hospital Kunming 650102 China

Funding

National Natural Science Foundation of China

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