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阿尔茨海默病患者内嗅皮质的免疫浸润情况

Landscape of immune infiltration in entorhinal cortex of patients with Alzheimer's disease.

作者信息

Zhang Hui, Cao Silu, Xu Yaru, Sun Xiaoru, Fei Miaomiao, Jing Qi, Xu Xiaodong, Tang Jinxuan, Niu Bing, Li Cheng

机构信息

Department of Anesthesiology and Perioperative Medicine, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, China.

Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Shanghai, China.

出版信息

Front Pharmacol. 2022 Sep 28;13:941656. doi: 10.3389/fphar.2022.941656. eCollection 2022.

Abstract

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases and manifests as progressive memory loss and cognitive dysfunction. Neuroinflammation plays an important role in the development of Alzheimer's disease and anti-inflammatory drugs reduce the risk of the disease. However, the immune microenvironment in the brains of patients with Alzheimer's disease remains unclear, and the mechanisms by which anti-inflammatory drugs improve Alzheimer's disease have not been clearly elucidated. This study aimed to provide an overview of the immune cell composition in the entorhinal cortex of patients with Alzheimer's disease based on the transcriptomes and signature genes of different immune cells and to explore potential therapeutic targets based on the relevance of drug targets. Transcriptomics data from the entorhinal cortex tissue, derived from GSE118553, were used to support our study. We compared the immune-related differentially expressed genes (irDEGs) between patients and controls by using the limma R package. The difference in immune cell composition between patients and controls was detected the xCell algorithm based on the marker genes in immune cells. The correlation between marker genes and immune cells and the interaction between genes and drug targets were evaluated to explore potential therapeutic target genes and drugs. There were 81 irDEGs between patients and controls that participated in several immune-related pathways. xCell analysis showed that most lymphocyte scores decreased in Alzheimer's disease, including CD4 Tc, CD4 Te, Th1, natural killer (NK), natural killer T (NKT), pro-B cells, eosinophils, and regulatory T cells, except for Th2 cells. In contrast, most myeloid cell scores increased in patients, except in dendritic cells. They included basophils, mast cells, plasma cells, and macrophages. Correlation analysis suggested that 37 genes were associated with these cells involved in innate immunity, of which eight genes were drug targets. Taken together, these results delineate the profile of the immune components of the entorhinal cortex in Alzheimer's diseases, providing a new perspective on the development and treatment of Alzheimer's disease.

摘要

阿尔茨海默病(AD)是最常见的神经退行性疾病之一,表现为进行性记忆丧失和认知功能障碍。神经炎症在阿尔茨海默病的发展中起重要作用,抗炎药物可降低该病的风险。然而,阿尔茨海默病患者大脑中的免疫微环境仍不清楚,抗炎药物改善阿尔茨海默病的机制也尚未明确阐明。本研究旨在基于不同免疫细胞的转录组和特征基因,概述阿尔茨海默病患者内嗅皮质中的免疫细胞组成,并根据药物靶点的相关性探索潜在的治疗靶点。来自GSE118553的内嗅皮质组织的转录组学数据用于支持我们的研究。我们使用limma R包比较了患者和对照组之间的免疫相关差异表达基因(irDEG)。基于免疫细胞中的标记基因,使用xCell算法检测患者和对照组之间免疫细胞组成的差异。评估标记基因与免疫细胞之间的相关性以及基因与药物靶点之间的相互作用,以探索潜在的治疗靶基因和药物。患者和对照组之间有81个irDEG参与了多个免疫相关途径。xCell分析表明,除Th2细胞外,阿尔茨海默病中大多数淋巴细胞评分降低,包括CD4 Tc、CD4 Te、Th1、自然杀伤(NK)细胞、自然杀伤T(NKT)细胞、前B细胞、嗜酸性粒细胞和调节性T细胞。相比之下,除树突状细胞外,患者中大多数髓样细胞评分增加。它们包括嗜碱性粒细胞、肥大细胞、浆细胞和巨噬细胞。相关性分析表明,37个基因与这些参与固有免疫的细胞相关,其中8个基因是药物靶点。综上所述,这些结果描绘了阿尔茨海默病内嗅皮质免疫成分的概况,为阿尔茨海默病的发展和治疗提供了新的视角。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9af8/9557331/0e45eeba8d79/fphar-13-941656-g001.jpg

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