ORIGINAL RESEARCH article
Front. Cardiovasc. Med.
Sec. Cardiovascular Genetics and Systems Medicine
Single cell RNA Sequencing Reveals a Dysbalance of Proinflammatory versus Immunosuppressive Dendritic Cells in Mouse and Human Aortic Aneurysms
Provisionally accepted
Yi Ran1Jingpu Zhu1Ting Sun1Yixin Zhang2
Chuankai Zhang1Yutao Li2Zhipeng Li1Shu Wang1Liping Li1
Junjie Zheng2
Changjun Yin1*Andreas J.R. Habenicht3*
Zhihua Wang1*- 1The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- 2Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians-University (LMU), Munich, Germany
- 3Nanjing Key Laboratory for Cardiovascular Information and Health Engineering Medicine, Institute of Clinical Medicine, Nanjing Drum Tower Hospital, Nanjing University, Nanjing, China
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Immune cell-driven destruction of the aortic wall remains a major contributor of death in patients burdened with aortic aneurysms (AAs). Dendritic cells (DCs) play critical roles in bridging innate and adaptive immunity by orchestrating robust inflammatory responses and concomitantly sustaining immune tolerance. However, the specific roles of DCs in AA pathogenesis remain to be explored. To examine the participation of DCs in AA pathogenesis, we used single-cell RNA sequencing (scRNA-seq) integration analyses to characterize DC heterogeneity and elucidate their putative involvement in AA pathogenesis in several mouse AA models and translate the experimental data to human AAs. Our data reveal that conventional DC2s (cDC2s) constituted the most abundant DC subtypes in both murine and human AAs. Furthermore, cDC1s, plasmacytoid DCs (pDCs) and immunosuppressive mature regulatory DCs (mregDCs) were identified. Within the cDC2 subtypes, the AA tissue environment trained cDC2s and a newly defined DC3s subtype toward highly pro-inflammatory phenotypes. Parallel to the increased prevalence of pro-inflammatory activated cDC2s and DC3s, a significant reduction of the number of mregDCs was observed in mouse AAs. This data revealed that the balance between pro-versus the anti-inflammatory DCs is disrupted in mouse AAs. Thus, therapeutic reconstitution strategies to correct this dysbalance together with protective measures that are already in use in clinical practice may lead to beneficial AA outcomes before surgical intervention is needed.
Keywords: Aortic Aneurysm, Dendritic Cells, Inflammation, Immunosuppression, Dysbalance
Received: 25 Sep 2025; Accepted: 04 Nov 2025.
Copyright: © 2025 Ran, Zhu, Sun, Zhang, Zhang, Li, Li, Wang, Li, Zheng, Yin, Habenicht and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Changjun Yin, yinchj3@mail.sysu.edu.cn
Andreas J.R. Habenicht, andreas.habenicht@njglyy.com
Zhihua Wang, wangzhh225@mail.sysu.edu.cn
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