Aortic aneurysms are characterized by vascular inflammation, neovascularization, and extracellular matrix destruction of the aortic wall. Although experimental studies indicate a potential role of CD248 in microvessel remodeling, the functions of CD248 in human vascular pathologies remain unexplored. Here we aimed to study how CD248 interferes with pathological vascular remodeling of human aortic aneurysms. Immunofluorescent staining showed that CD248 expression was mainly localized in the CD8+ T cells infiltrating in the adventitia and media of aortic walls of patients with ascending thoracic aortic aneurysms. qPCR and immunofluorescent staining analyses revealed increased aortic CD248 expression and infiltrating CD248+CD8+ T cells in aortic aneurysms than in nonaneurysmal aortas. Flow cytometry analysis of human peripheral blood further identified a fraction of circulating CD248+ cells which was confined in the CD8+ T-cell compartment. The increased infiltrating of CD248+CD8+ T cells was coincident with reduced circulating CD248+CD8+ T cells in patients with ascending TAA when compared with patients with coronary artery diseases and healthy donors. The CD248+CD8+ T cells were characterized by upregulated IL-10 and downregulated IL-1β/INF-γ expression when compared with CD248-CD8+ T cells. Moreover, when co-cultured with human aortic endothelial cells, the CD248+CD8+ T cells not only downregulated endothelial expression of ICAM1/VCAM1 and MMP2/3 but also suppressed endothelial migration. This study shows that CD248 reduces pathological vascular remodeling via anti-inflammatory CD248+CD8+ T cells, revealing a CD248-mediated cellular mechanism against human aortic aneurysms.

Impact statement

In spite of recent evidence indicating that CD248 is linked to microvasculature remodeling, immune response, and MMP activity, the functions of CD248 in human TAA remain unexplored. In this work, by analyzing cellular components of in situ as well as of blood circulation of human TAA, we have identified a novel T cell subset, the CD248+CD8+ T cells, which exhibits anti-inflammatory properties, and that we have also provided the first evidence that these cells not only suppress endothelial expression of ICAM1/VCAM1 and MMP2/3, but also inhibit endothelial migration, thus uncovering a CD248-mediated cellular mechanism against pathological vascular remodeling in human aortic aneurysms.

中文翻译：

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CD248+CD8+T 淋巴细胞抑制人胸主动脉瘤的病理性血管重塑。

主动脉瘤的特征在于主动脉壁的血管炎症、新生血管形成和细胞外基质破坏。尽管实验研究表明 CD248 在微血管重塑中的潜在作用，但 CD248 在人类血管病理中的功能仍未得到探索。在这里，我们旨在研究 CD248 如何干扰人类主动脉瘤的病理性血管重塑。免疫荧光染色显示CD248的表达主要定位于浸润在胸升主动脉瘤患者主动脉壁外膜和中膜的CD8+T细胞。qPCR 和免疫荧光染色分析显示，与非动脉瘤主动脉相比，主动脉瘤中主动脉 CD248 表达增加和浸润 CD248+CD8+T 细胞。人外周血的流式细胞术分析进一步鉴定了一部分循环 CD248+ 细胞，其被限制在 CD8+ T 细胞隔室中。与冠状动脉疾病患者和健康供体相比，升高的 TAA 患者中 CD248+CD8+T 细胞浸润增加与循环 CD248+CD8+T 细胞减少一致。与 CD248-CD8+T 细胞相比，CD248+CD8+T 细胞的特征是 IL-10 上调和 IL-1β/INF-γ 表达下调。此外，当与人主动脉内皮细胞共培养时，CD248+CD8+T 细胞不仅下调 ICAM1/VCAM1 和 MMP2/3 的内皮表达，而且抑制内皮迁移。该研究表明，CD248 通过抗炎 CD248+CD8+T 细胞减少病理性血管重塑，

影响陈述

尽管最近有证据表明 CD248 与微血管系统重构、免疫反应和 MMP 活性有关，但 CD248 在人类 TAA 中的功能仍未得到探索。在这项工作中，通过分析原位以及人类 TAA 血液循环的细胞成分，我们确定了一个新的 T 细胞亚群，CD248+CD8+T 细胞，它具有抗炎特性，并且我们还提供了第一个证据表明，这些细胞不仅抑制 ICAM1/VCAM1 和 MMP2/3 的内皮表达，而且抑制内皮迁移，从而揭示了 CD248 介导的抗人主动脉瘤病理性血管重塑的细胞机制。