在多发性硬化症小鼠模型中,循环髓源性抑制细胞负荷和疾病严重程度与少突胶质细胞产生增强有关

IF 5.1 2区 医学 Q1 NEUROSCIENCES
Mari Paz Serrano-Regal , Celia Camacho-Toledano , Inmaculada Alonso-García , María Cristina Ortega , Isabel Machín-Díaz , Rafael Lebrón-Galán , Jénnifer García-Arocha , Leticia Calahorra , Manuel Nieto-Díaz , Diego Clemente
{"title":"在多发性硬化症小鼠模型中,循环髓源性抑制细胞负荷和疾病严重程度与少突胶质细胞产生增强有关","authors":"Mari Paz Serrano-Regal ,&nbsp;Celia Camacho-Toledano ,&nbsp;Inmaculada Alonso-García ,&nbsp;María Cristina Ortega ,&nbsp;Isabel Machín-Díaz ,&nbsp;Rafael Lebrón-Galán ,&nbsp;Jénnifer García-Arocha ,&nbsp;Leticia Calahorra ,&nbsp;Manuel Nieto-Díaz ,&nbsp;Diego Clemente","doi":"10.1016/j.nbd.2025.106919","DOIUrl":null,"url":null,"abstract":"<div><div>Multiple sclerosis (MS) is a highly heterogeneous immune-mediated demyelinating disease. Myelin restoration is essential to prevent disability progression in MS patients. However, remyelinating therapies are failing in clinical trials, in part, due to the lack of biomarkers that classify the differing endogenous regenerative capacities of enrolled patients. In the experimental autoimmune encephalomyelitis (EAE) MS model, circulating monocytic myeloid-derived suppressor cells (M-MDSCs) are associated to milder disease courses, better recovery and less degree of tissue damage. Here, we show that disease severity affects the gradient of oligodendrocyte precursor cells (OPCs) present in mixed active-inactive lesions of MS patients, along with a positive correlation between M-MDSC density and OPC abundance. EAE disease severity negatively influences the density of total and newly generated OPCs found associated to the demyelinated lesions. In addition, disease severity also impacts the abundance of newly generated oligodendrocytes throughout the EAE disease course. Interestingly, circulating M-MDSCs at EAE onset and peak of the disease are directly associated to a higher density of newly generated oligodendrocytes in the demyelinated lesions. Our results set the basis for further studies on M-MDSCs as a promising new biomarker that identify a CNS prone to new oligodendrocyte generation in response to an inflammatory insult.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"210 ","pages":"Article 106919"},"PeriodicalIF":5.1000,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Circulating myeloid-derived suppressor cell load and disease severity are associated to an enhanced oligodendroglial production in a murine model of multiple sclerosis\",\"authors\":\"Mari Paz Serrano-Regal ,&nbsp;Celia Camacho-Toledano ,&nbsp;Inmaculada Alonso-García ,&nbsp;María Cristina Ortega ,&nbsp;Isabel Machín-Díaz ,&nbsp;Rafael Lebrón-Galán ,&nbsp;Jénnifer García-Arocha ,&nbsp;Leticia Calahorra ,&nbsp;Manuel Nieto-Díaz ,&nbsp;Diego Clemente\",\"doi\":\"10.1016/j.nbd.2025.106919\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Multiple sclerosis (MS) is a highly heterogeneous immune-mediated demyelinating disease. Myelin restoration is essential to prevent disability progression in MS patients. However, remyelinating therapies are failing in clinical trials, in part, due to the lack of biomarkers that classify the differing endogenous regenerative capacities of enrolled patients. In the experimental autoimmune encephalomyelitis (EAE) MS model, circulating monocytic myeloid-derived suppressor cells (M-MDSCs) are associated to milder disease courses, better recovery and less degree of tissue damage. Here, we show that disease severity affects the gradient of oligodendrocyte precursor cells (OPCs) present in mixed active-inactive lesions of MS patients, along with a positive correlation between M-MDSC density and OPC abundance. EAE disease severity negatively influences the density of total and newly generated OPCs found associated to the demyelinated lesions. In addition, disease severity also impacts the abundance of newly generated oligodendrocytes throughout the EAE disease course. Interestingly, circulating M-MDSCs at EAE onset and peak of the disease are directly associated to a higher density of newly generated oligodendrocytes in the demyelinated lesions. Our results set the basis for further studies on M-MDSCs as a promising new biomarker that identify a CNS prone to new oligodendrocyte generation in response to an inflammatory insult.</div></div>\",\"PeriodicalId\":19097,\"journal\":{\"name\":\"Neurobiology of Disease\",\"volume\":\"210 \",\"pages\":\"Article 106919\"},\"PeriodicalIF\":5.1000,\"publicationDate\":\"2025-04-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Neurobiology of Disease\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0969996125001354\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neurobiology of Disease","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0969996125001354","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
引用次数: 0

摘要

多发性硬化症(MS)是一种高度异质性免疫介导的脱髓鞘疾病。髓磷脂修复对于预防多发性硬化症患者残疾进展至关重要。然而,髓鞘再生疗法在临床试验中失败,部分原因是缺乏对入组患者不同内源性再生能力进行分类的生物标志物。在实验性自身免疫性脑脊髓炎(EAE) MS模型中,循环单核细胞髓源性抑制细胞(M-MDSCs)与病程较轻、恢复较好和组织损伤程度较小相关。在这里,我们发现疾病严重程度影响MS患者混合活性-非活性病变中少突胶质前体细胞(OPC)的梯度,以及M-MDSC密度与OPC丰度之间的正相关。EAE疾病严重程度对与脱髓鞘病变相关的总OPCs和新生成OPCs的密度产生负面影响。此外,在整个EAE病程中,疾病严重程度也会影响新生成的少突胶质细胞的丰度。有趣的是,在EAE发病和疾病高峰时循环的M-MDSCs与脱髓鞘病变中新生成的少突胶质细胞密度较高直接相关。我们的研究结果为进一步研究M-MDSCs作为一种有前景的新生物标志物奠定了基础,该标志物可识别炎症损伤后中枢神经系统中容易产生新少突胶质细胞的生物标志物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Circulating myeloid-derived suppressor cell load and disease severity are associated to an enhanced oligodendroglial production in a murine model of multiple sclerosis
Multiple sclerosis (MS) is a highly heterogeneous immune-mediated demyelinating disease. Myelin restoration is essential to prevent disability progression in MS patients. However, remyelinating therapies are failing in clinical trials, in part, due to the lack of biomarkers that classify the differing endogenous regenerative capacities of enrolled patients. In the experimental autoimmune encephalomyelitis (EAE) MS model, circulating monocytic myeloid-derived suppressor cells (M-MDSCs) are associated to milder disease courses, better recovery and less degree of tissue damage. Here, we show that disease severity affects the gradient of oligodendrocyte precursor cells (OPCs) present in mixed active-inactive lesions of MS patients, along with a positive correlation between M-MDSC density and OPC abundance. EAE disease severity negatively influences the density of total and newly generated OPCs found associated to the demyelinated lesions. In addition, disease severity also impacts the abundance of newly generated oligodendrocytes throughout the EAE disease course. Interestingly, circulating M-MDSCs at EAE onset and peak of the disease are directly associated to a higher density of newly generated oligodendrocytes in the demyelinated lesions. Our results set the basis for further studies on M-MDSCs as a promising new biomarker that identify a CNS prone to new oligodendrocyte generation in response to an inflammatory insult.
求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Neurobiology of Disease
Neurobiology of Disease 医学-神经科学
CiteScore
11.20
自引率
3.30%
发文量
270
审稿时长
76 days
期刊介绍: Neurobiology of Disease is a major international journal at the interface between basic and clinical neuroscience. The journal provides a forum for the publication of top quality research papers on: molecular and cellular definitions of disease mechanisms, the neural systems and underpinning behavioral disorders, the genetics of inherited neurological and psychiatric diseases, nervous system aging, and findings relevant to the development of new therapies.
×
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