Single-Cell Sequencing of Immune Cells in Human Aortic Dissection Tissue Provides Insights Into Immune Cell Heterogeneity.
Single-Cell Sequencing of Immune Cells in Human Aortic Dissection Tissue Provides Insights Into Immune Cell Heterogeneity.
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DOI：
10.3389/fcvm.2022.791875
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发表时间：
2022
影响因子：
3.6
通讯作者：
中科院分区：
文献类型：
--
作者：
炎症在散发性主动脉夹层（AD）的进展中起重要作用。免疫细胞，特别是巨噬细胞，浸润主动脉并分泌炎性细胞因子和基质金属蛋白酶，引起细胞外基质降解，从而促进AD的发病机制。然而，这些免疫细胞内的细胞异质性尚未完全表征。我们使用单细胞RNA测序来分析AD组织和正常主动脉中所有免疫细胞的转录组。使用CD 45上的磁激活细胞分选门控，我们获得了主动脉中免疫细胞亚群的更高分辨率鉴定。我们观察到AD和正常主动脉组织中主要免疫细胞亚群的比例存在显著差异。AD组织中T细胞、B细胞和自然杀伤（NK）细胞比例均增高。在AD组织中扩增的巨噬细胞簇主要来源于循环单核细胞，并表达编码促炎细胞因子和参与组织修复的分子的基因。AD组织中的T细胞和NK细胞表现出增强的细胞毒性。AD组织中大量扩增的CD 4 + T细胞具有Th 17样细胞的特征，可能与AD的发病机制有关。细胞-细胞相互作用分析强调了巨噬细胞和T细胞之间的通信增加，其主要调节T细胞的共刺激。我们的研究提供了一个全面的表征免疫细胞在主动脉夹层的作用，重点是巨噬细胞和T细胞。我们研究的信息提高了我们对AD形成中免疫机制的理解，并有助于确定早期诊断或治疗AD的其他有用靶点。
Inflammation plays an important role in the progression of sporadic aortic dissection (AD). Immune cells, especially macrophages, infiltrate the aorta and secrete inflammatory cytokines and matrix metalloproteinases to cause degradation of the extracellular matrix, thereby contributing to the pathogenesis of AD. However, the cellular heterogeneity within these immune cells has not been fully characterized. We used single-cell RNA sequencing to profile the transcriptomes of all immune cells in AD tissue and normal aorta. Using magnetic-activated cell sorting gating on CD45, we obtained a higher resolution identification of the immune cell subsets in the aorta. We observed significant differences in the proportion of major immune cell subpopulations between AD and normal aorta tissues. Macrophages accounted for a higher percentage in the normal aorta, while the proportions of T cells, B cells and natural killer (NK) cells were all increased in AD tissues. Macrophage clusters that expanded in AD tissues originated primarily from circulating monocytes and expressed genes encoding proinflammatory cytokines and molecules involved in tissue repair. T and NK cells in AD tissues exhibited enhanced cytotoxic properties. A cluster of CD4+ T cells that had expanded in AD tissues was Th17-like and might contribute to the pathogenesis of AD. Cell–cell interaction analysis highlighted the increased communication between macrophages and T cells, which primarily regulated the costimulation of T cells. Our study provides a comprehensive characterization of immune cells in the dissected aorta with an emphasis on the role of macrophages and T cells. The information from our study improves our understanding of immune mechanisms in AD formation and helps to identify additional useful targets for early diagnosis or therapy of AD.
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影响因子：
6.4
作者：
Collin M;Bigley V
通讯作者：
Bigley V
影响因子：
4.6
作者：
Khawar MB;Abbasi MH;Sheikh N
通讯作者：
Sheikh N
RER诱导干扰素调节因子4（IRF-4）在淋巴细胞中的表达：通过REL/核因子Kappab对干扰素调节的基因表达的调节。
影响因子：
15.3
作者：
Grumont, R J;Gerondakis, S
通讯作者：
Gerondakis, S
DOI：
10.1161/atvbaha.120.313584
发表时间：
2021-03
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Khoury MK;Yang H;Liu B
通讯作者：
Liu B
影响因子：
32.4
作者：
Escobar, Thelma M.;Kanellopoulou, Chrysi;Kugler, David G.;Kilaru, Gokhul;Nguyen, Cuong K.;Nagarajan, Vijayaraj;Bhairavabhotla, Ravikiran K.;Northrup, Daniel;Zahr, Rami;Burr, Patrick;Liu, Xiuhuai;Zhao, Keji;Sher, Alan;Jankovic, Dragana;Zhu, Jinfang;Muljo, Stefan A.
通讯作者：
Muljo, Stefan A.