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老年鼠大脑皮层小胶质细胞呈现出一种可能具有免疫耐受功能的激活状态。

Aged Mouse Cortical Microglia Display an Activation Profile Suggesting Immunotolerogenic Functions.

机构信息

Institute for Anatomy and Cell Biology, Department of Molecular Embryology, Faculty of Medicine, University of Freiburg, Freiburg 79104, Germany.

Faculty of Biology, University of Freiburg, Freiburg 79104, Germany.

出版信息

Int J Mol Sci. 2018 Mar 1;19(3):706. doi: 10.3390/ijms19030706.

DOI:10.3390/ijms19030706
PMID:29494550
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5877567/
Abstract

Microglia are the resident immune cells of the central nervous system (CNS) and participate in physiological and pathological processes. Their unique developmental nature suggests age-dependent structural and functional impairments that might contribute to neurodegenerative diseases. In the present study, we addressed the age-dependent changes in cortical microglia gene expression patterns and the expression of M1- and M2-like activation markers. Iba1 immunohistochemistry, isolation of cortical microglia followed by fluorescence-activated cell sorting and RNA isolation to analyze transcriptional changes in aged cortical microglia was performed. We provide evidence that aging is associated with decreased numbers of cortical microglia and the establishment of a distinct microglia activation profile including upregulation of , , , , and . Moreover, flow cytometry revealed that aged cortical microglia express increased levels of Cd206 and Cd36. The data presented in the current study indicate that aged mouse cortical microglia adopt a distinct activation profile, which suggests immunosuppressive and immuno-tolerogenic functions.

摘要

小胶质细胞是中枢神经系统(CNS)的固有免疫细胞,参与生理和病理过程。它们独特的发育特性表明存在与年龄相关的结构和功能障碍,这可能导致神经退行性疾病。在本研究中,我们研究了皮质小胶质细胞基因表达模式和 M1 样和 M2 样激活标志物表达的年龄依赖性变化。通过 Iba1 免疫组织化学、皮质小胶质细胞的分离,然后进行荧光激活细胞分选和 RNA 分离,分析衰老皮质小胶质细胞的转录变化。我们提供的证据表明,衰老与皮质小胶质细胞数量减少以及独特的小胶质细胞激活谱的建立有关,包括上调 、 、 、 、 。此外,流式细胞术显示,衰老的皮质小胶质细胞表达更高水平的 Cd206 和 Cd36。本研究中提供的数据表明,衰老的小鼠皮质小胶质细胞表现出独特的激活谱,提示其具有免疫抑制和免疫耐受功能。

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Immunity. 2018 Mar 20;48(3):599. doi: 10.1016/j.immuni.2018.02.014.
2
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Nat Commun. 2018 Feb 7;9(1):539. doi: 10.1038/s41467-018-02926-5.
3
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Aging Cell. 2025 May;24(5):e14491. doi: 10.1111/acel.14491. Epub 2025 Feb 2.
4
Brain-wide cell-type-specific transcriptomic signatures of healthy ageing in mice.小鼠健康衰老的全脑细胞类型特异性转录组特征
Nature. 2025 Feb;638(8049):182-196. doi: 10.1038/s41586-024-08350-8. Epub 2025 Jan 1.
5
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6
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Brain Behav Immun. 2024 Aug;120:439-451. doi: 10.1016/j.bbi.2024.06.023. Epub 2024 Jun 24.
7
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4
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9
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Glia. 2017 Sep;65(9):1397-1406. doi: 10.1002/glia.23154. Epub 2017 May 18.
10
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