Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
China National Clinical Research Center for Neurological Diseases, Beijing, China.
Front Immunol. 2022 Jun 27;13:922000. doi: 10.3389/fimmu.2022.922000. eCollection 2022.
Increasing evidence supports a critical role of chronic inflammation in intracranial aneurysm (IA). Understanding how the immunological alterations in IA provides opportunities for targeted treatment. However, there is a lack of comprehensive and detailed characterization of the changes in circulating immune cells in IA.
To perform a comprehensive and detailed characterization of the changes in circulating immune cells in patients with IA.
Peripheral blood mononuclear cell samples from IA patients (n = 26) and age-and sex-matched healthy controls (HCs, n = 20) were analyzed using high dimensional mass cytometry, and the frequency and phenotype of immune cell subtypes were assessed.
We identified 28 cell clusters and found that the immune signature of IA consists of cluster changes. IA patients exhibited dysfunction of immunity, with dysregulation of CD4 T-cell clusters, increased B cells and monocytes, and decreased CD8 T cells, DNT cells, and DPT cells. Moreover, compared with findings in HC, IA was associated with enhanced lymphocyte and monocyte immune activation, with a higher expression of HLA-DR, CXCR3, and CX3CR1. In addition, the expression of TLR4, p-STAT3, and the exhaustion marker PD1 was increased in T cells, B cells, and NK cells in IA patients.
Our data provide an overview of the circulating immune cell landscape of IA patients, and reveal that the dysfunction of circulating immunity may play a potential role in the development of IA.
越来越多的证据支持慢性炎症在颅内动脉瘤(IA)中的关键作用。了解 IA 中免疫改变的机制为靶向治疗提供了机会。然而,IA 患者循环免疫细胞变化的全面和详细特征描述仍然缺乏。
全面详细地描述 IA 患者循环免疫细胞的变化。
采用高维液质流式细胞术分析 IA 患者(n=26)和年龄及性别匹配的健康对照者(HCs,n=20)的外周血单个核细胞样本,评估免疫细胞亚群的频率和表型。
我们鉴定出 28 个细胞簇,发现 IA 的免疫特征由簇变化组成。IA 患者表现出免疫功能障碍,CD4 T 细胞簇失调,B 细胞和单核细胞增加,CD8 T 细胞、DN T 细胞和 DP T 细胞减少。此外,与 HC 相比,IA 与淋巴细胞和单核细胞免疫激活增强相关,HLA-DR、CXCR3 和 CX3CR1 的表达更高。此外,IA 患者 T 细胞、B 细胞和 NK 细胞中 TLR4、p-STAT3 和耗竭标志物 PD1 的表达增加。
我们的数据提供了 IA 患者循环免疫细胞图谱的概述,并表明循环免疫功能障碍可能在 IA 的发展中起潜在作用。