Single-cell Characterization Of The Immune Microenvironment Of Abdominal Aortic Aneurysm

Background: Abdominal aortic aneurysm (AAA), characterized by localized dilation of the abdominal aorta, involves an immune microenvironment that plays a crucial role in disease development. This study aimed to investigate immune cell heterogeneity and functional dynamics in AAA using single-cell RNA sequencing (scRNA-seq) analysis of AAA content and healthy aorta samples.
Methods: By analyzing scRNA-seq datasets from AAA content and healthy aorta samples, along with bulk datasets comprising AAA and healthy aortic tissues, we comprehensively profiled the immune microenvironment.
Results: The analysis revealed five major cell types in both AAA contents and healthy aortic tissues. Further integrative analysis identified 18 distinct subpopulations, unraveling specific immune cell subtypes within AAA. These subtypes were distinguished based on tissue infiltration, functional variations, immune dynamics, metabolic changes, and communication patterns. Notably, B cells and plasma cells were found to contribute to AAA and thrombus formation. Additionally, cytotoxic CD8+ T cells showed enrichment in cytokine and chemokine receptor interactions, indicating their involvement in AAA development. Two pro-inflammatory macrophage subtypes (LY6E+ and CCL5+) and two pro-inflammatory neutrophil subtypes specific to AAA emerged as significant findings. Particularly, MME+ neutrophils exhibited heightened immune receptor activity and infiltrated AAA tissues, as supported by bulk dataset analysis. Metabolically active, these neutrophils played a vital role in regulating CXCL signaling, enabling effective cell-to-cell communication among immune cells.
Conclusions: This study provides a comprehensive understanding of the diverse immune cell populations within AAA and healthy aorta tissues. The findings shed light on their functional characteristics, developmental trajectories, metabolic differences, and intercellular communication patterns, significantly advancing our knowledge of AAA formation and progression.

背景：腹主动脉瘤（AAA），以其在腹主动脉的局部扩张为特征，其疾病发展涉及一个在疾病发生中扮演关键角色的免疫微环境。本研究旨在通过分析腹主动脉瘤内容物和健康主动脉样本的单细胞RNA测序（scRNA-seq）数据，以及包括AAA和健康主动脉组织的批量数据集，来研究AAA中的免疫细胞异质性和功能动态。方法：通过分析来自AAA内容物和健康主动脉样本的scRNA-seq数据集，以及包括AAA和健康主动脉组织的批量数据集，我们全面地描绘了免疫微环境。结果：分析揭示了在AAA内容物和健康主动脉组织中均存在五种主要细胞类型。进一步的综合分析识别出18个不同的亚群，揭示了AAA内部的特定免疫细胞亚型。这些亚型根据组织浸润、功能变化、免疫动力学、代谢变化和通讯模式进行区分。值得注意的是，B细胞和浆细胞被发现与AAA和血栓形成有关。此外，细胞毒性CD8+ T细胞在细胞因子和趋化因子受体相互作用中富集，表明其在AAA发展中的作用。两种促炎巨噬细胞亚型（LY6E+和CCL5+）以及两种特异于AAA的促炎中性粒细胞亚型成为显著发现。特别是，MME+中性粒细胞表现出增强的免疫受体活性，并浸润AAA组织，如批量数据集分析所支持。代谢活跃的中性粒细胞在调节CXCL信号传导中发挥了至关重要的作用，使免疫细胞之间的细胞间通讯有效进行。结论：本研究对AAA和健康主动脉组织中的多种免疫细胞群体提供了全面的理解。研究结果揭示了它们的生物学特性、发育轨迹、代谢差异和细胞间通讯模式，显著推进了我们对AAA形成和发展的认识。