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单细胞图谱分析动脉粥样硬化患者的细胞因子:循环和局部免疫紊乱。

Single-Cell Atlas of Atherosclerosis Patients by Cytof: Circulatory and Local Immune Disorders.

机构信息

Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

China National Clinical Research Center for Neurological Diseases, Beijing, China.

出版信息

Aging Dis. 2024 Feb 1;15(1):245-258. doi: 10.14336/AD.2023.0426-1.

Abstract

Atherosclerosis (AS) is a common underlying pathology of coronary artery disease, peripheral artery disease, and stroke. The characteristics of immune cells within plaques and their functional relationships with blood are crucial in AS. In this study, Mass cytometry (CyTOF), RNA-sequencing and immunofluorescence were combined to comprehensively analyze plaque tissues and peripheral blood from 25 AS patients (22 for Mass cytometry and 3 for RNA-sequencing), as well as blood from 20 healthy individuals. The study identified a complexity of leukocytes in the plaque, including both defined anti-inflammatory and pro-inflammatory subsets such as M2-like CD163+ macrophages, Natural killer T cells (NKT), CD11b+ CD4+ T effector memory cells (Tem), and CD8+ terminally differentiated effector memory cells (TEMRA). Functionally activated cell subsets were also found in peripheral blood in AS patients, highlighting the vivid interactions between leukocytes in plaque and blood. The study provides an atlas of the immune landscape in atherosclerotic patients, where pro-inflammatory activation was found to be a major feature of peripheral blood. The study identified NKT, CD11b+ CD4+ Tem, CD8+ TEMRA and CD163+ macrophages as key players in the local immune environment.

摘要

动脉粥样硬化(AS)是冠状动脉疾病、外周动脉疾病和中风的常见潜在病理。斑块内免疫细胞的特征及其与血液的功能关系在 AS 中至关重要。在这项研究中,质谱流式细胞术(CyTOF)、RNA 测序和免疫荧光相结合,全面分析了 25 名 AS 患者(22 名用于质谱流式细胞术,3 名用于 RNA 测序)和 20 名健康个体的斑块组织和外周血。该研究确定了斑块中白细胞的复杂性,包括定义明确的抗炎和促炎亚群,如 M2 样 CD163+巨噬细胞、自然杀伤 T 细胞(NKT)、CD11b+CD4+T 效应记忆细胞(Tem)和 CD8+终末分化效应记忆细胞(TEMRA)。在 AS 患者的外周血中也发现了功能激活的细胞亚群,突出了白细胞在斑块和血液之间的生动相互作用。该研究提供了动脉粥样硬化患者免疫图谱,其中促炎激活是外周血的主要特征。该研究确定了 NKT、CD11b+CD4+ Tem、CD8+TEMRA 和 CD163+巨噬细胞是局部免疫环境中的关键参与者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ce9/10796097/673347cf8f98/AD-15-1-245-g1.jpg

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