IL-17A promotes the progression of Alzheimer’s disease in APP/PS1 mice

IF 5.2 2区 医学 Q1 GERIATRICS & GERONTOLOGY
Min Cao, Jing Liu, Xiaomin Zhang, Yaqi Wang, Yuli Hou, Qiao Song, Yuting Cui, Yue Zhao, Peichang Wang
{"title":"IL-17A promotes the progression of Alzheimer’s disease in APP/PS1 mice","authors":"Min Cao, Jing Liu, Xiaomin Zhang, Yaqi Wang, Yuli Hou, Qiao Song, Yuting Cui, Yue Zhao, Peichang Wang","doi":"10.1186/s12979-023-00397-x","DOIUrl":null,"url":null,"abstract":"Alzheimer’s disease (AD), which is the most common cause of dementia in elderly individuals, is a progressive neurodegenerative disorder. Neuroinflammation, which is an immune response that is activated by glial cells in the central nervous system, plays an important role in neurodegenerative diseases. Many studies have shown that interleukin-17A (IL-17A) plays an important role in AD, but research on the pathological effects of IL-17A on AD is limited. We report the effect of IL-17A on AD progression in APPswe/PS1dE9 (APP/PS1) mice, which are the most widely used AD model mice. The BV2 cell line, which is a microglial cell line derived from C57/BL6 mice, was used to establish a cell model to verify the role of IL-17A in neuroinflammation at the cellular level. The HT22 hippocampal neuronal cell line was used to investigate the relationship between IL-17A and Aβ deposition. In this research, we found that IL-17A promotes the progression of AD in the APP/PS1 mouse model. The role of IL-17A in neuroinflammation is related to tumour necrosis factor (TNF)-α. Circulating IL-17A stimulates the secretion of TNF-α by microglia through the Toll-like receptor 4 (TLR4)/nuclear factor (NF)-κB signalling pathway, thus exacerbating neuroinflammation. In addition, intraperitoneal injection of IL-17A antibody (IL17Ab) significantly improved the cognitive function of APP/PS1 mice. IL-17A increased TNF-α levels in the brain and exacerbated neuroinflammation through the TLR4/NF-κB signalling pathway and microglial activation in APP/PS1 mice. Moreover, IL-17A promoted the progression of AD by enhancing neuroinflammation, inhibiting microglial phagocytosis, and promoting the deposition of β-amyloid 42 in AD model mice.","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":null,"pages":null},"PeriodicalIF":5.2000,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Immunity & Ageing","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12979-023-00397-x","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GERIATRICS & GERONTOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Alzheimer’s disease (AD), which is the most common cause of dementia in elderly individuals, is a progressive neurodegenerative disorder. Neuroinflammation, which is an immune response that is activated by glial cells in the central nervous system, plays an important role in neurodegenerative diseases. Many studies have shown that interleukin-17A (IL-17A) plays an important role in AD, but research on the pathological effects of IL-17A on AD is limited. We report the effect of IL-17A on AD progression in APPswe/PS1dE9 (APP/PS1) mice, which are the most widely used AD model mice. The BV2 cell line, which is a microglial cell line derived from C57/BL6 mice, was used to establish a cell model to verify the role of IL-17A in neuroinflammation at the cellular level. The HT22 hippocampal neuronal cell line was used to investigate the relationship between IL-17A and Aβ deposition. In this research, we found that IL-17A promotes the progression of AD in the APP/PS1 mouse model. The role of IL-17A in neuroinflammation is related to tumour necrosis factor (TNF)-α. Circulating IL-17A stimulates the secretion of TNF-α by microglia through the Toll-like receptor 4 (TLR4)/nuclear factor (NF)-κB signalling pathway, thus exacerbating neuroinflammation. In addition, intraperitoneal injection of IL-17A antibody (IL17Ab) significantly improved the cognitive function of APP/PS1 mice. IL-17A increased TNF-α levels in the brain and exacerbated neuroinflammation through the TLR4/NF-κB signalling pathway and microglial activation in APP/PS1 mice. Moreover, IL-17A promoted the progression of AD by enhancing neuroinflammation, inhibiting microglial phagocytosis, and promoting the deposition of β-amyloid 42 in AD model mice.
IL-17A 促进 APP/PS1 小鼠阿尔茨海默病的发展
阿尔茨海默病(AD)是一种进行性神经退行性疾病,是老年人痴呆症的最常见原因。神经炎症是一种由中枢神经胶质细胞激活的免疫反应,在神经退行性疾病中起着重要作用。许多研究表明,白细胞介素- 17a (IL-17A)在AD中起重要作用,但IL-17A对AD病理作用的研究有限。我们报道了IL-17A对应用最广泛的AD模型小鼠APPswe/PS1dE9 (APP/PS1)小鼠AD进展的影响。采用来源于C57/BL6小鼠的小胶质细胞系BV2建立细胞模型,从细胞水平验证IL-17A在神经炎症中的作用。采用HT22海马神经元细胞系研究IL-17A与Aβ沉积的关系。本研究中,我们发现IL-17A在APP/PS1小鼠模型中促进AD的进展。IL-17A在神经炎症中的作用与肿瘤坏死因子-α有关。循环IL-17A通过toll样受体4 (TLR4)/核因子(NF)-κB信号通路刺激小胶质细胞分泌TNF-α,从而加重神经炎症。此外,腹腔注射IL-17A抗体(IL17Ab)可显著改善APP/PS1小鼠的认知功能。在APP/PS1小鼠中,IL-17A通过TLR4/NF-κB信号通路和小胶质细胞激活增加脑内TNF-α水平,加重神经炎症。此外,IL-17A通过增强AD模型小鼠的神经炎症、抑制小胶质细胞吞噬、促进β-淀粉样蛋白42的沉积来促进AD的进展。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Immunity & Ageing
Immunity & Ageing GERIATRICS & GERONTOLOGY-IMMUNOLOGY
CiteScore
10.20
自引率
3.80%
发文量
55
期刊介绍: Immunity & Ageing is a specialist open access journal that was first published in 2004. The journal focuses on the impact of ageing on immune systems, the influence of aged immune systems on organismal well-being and longevity, age-associated diseases with immune etiology, and potential immune interventions to increase health span. All articles published in Immunity & Ageing are indexed in the following databases: Biological Abstracts, BIOSIS, CAS, Citebase, DOAJ, Embase, Google Scholar, Journal Citation Reports/Science Edition, OAIster, PubMed, PubMed Central, Science Citation Index Expanded, SCImago, Scopus, SOCOLAR, and Zetoc.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信