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在多发性硬化症小鼠模型中,短期暴露于颗粒物会引发血浆细胞外囊泡包裹的微小RNA的选择性改变。

Short-term exposure to particulate matter triggers a selective alteration of plasma extracellular vesicle-packaged miRNAs in a mouse model of multiple sclerosis.

作者信息

Bonato Martino, Cerrato Valentina, Dioni Laura, Montarolo Francesca, Parolisi Roberta, Bertolotto Antonio, Bollati Valentina, Ferrari Luca, Boda Enrica

机构信息

Neuroscience Institute Cavalieri Ottolenghi (NICO), Department of Neuroscience Rita Levi-Montalcini, University of Turin, Turin, Italy.

EPIGET LAB, Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.

出版信息

Front Immunol. 2025 Jul 3;16:1596935. doi: 10.3389/fimmu.2025.1596935. eCollection 2025.

DOI:10.3389/fimmu.2025.1596935
PMID:40677715
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12267195/
Abstract

Epidemiological studies have highlighted the existence of population groups exhibiting a higher sensitivity to the impact of environmental factors, such as exposure to air pollution. In these regards, people with Multiple Sclerosis (MS) or predisposed to develop MS - an autoimmune disorder of the Central Nervous System (CNS) - appear as a more vulnerable cohort to the effects of particulate matter (PM) exposure. Here, we aimed at disclosing the biological substrate of such higher vulnerability, and specifically at understanding whether individuals primed to develop autoimmunity (as it occurs in MS and in the experimental autoimmune encephalomyelitis - EAE - animal model of MS) respond differently to PM compared to healthy subjects. To this purpose, we characterized plasmatic extracellular vesicles (EVs) and their microRNA (miRNA) cargo in healthy and presymptomatic EAE mice early after exposure to PM, compared to unexposed healthy and EAE mice. Results showed that the response of EAE mice to PM did not differ in terms of EV number or source, compared to that of healthy mice. Yet, remarkable differences existed in the identity of deregulated EV-associated miRNAs, which, in EAE mice, were predicted to target several MS-relevant biological processes and nervous system-, immune- and inflammation-related pathways, possibly contributing to disease worsening.

摘要

流行病学研究强调了存在对环境因素影响更为敏感的人群群体,例如暴露于空气污染中。在这方面,患有多发性硬化症(MS)或易患MS(一种中枢神经系统(CNS)的自身免疫性疾病)的人似乎是对颗粒物(PM)暴露影响更脆弱的群体。在此,我们旨在揭示这种更高脆弱性的生物学基础,特别是了解那些准备发展为自身免疫性疾病的个体(如在MS以及MS的实验性自身免疫性脑脊髓炎——EAE——动物模型中发生的情况)与健康受试者相比,对PM的反应是否不同。为此,我们对暴露于PM后的健康和症状前EAE小鼠的血浆细胞外囊泡(EVs)及其微小RNA(miRNA)货物进行了表征,并与未暴露的健康和EAE小鼠进行了比较。结果表明,与健康小鼠相比,EAE小鼠对PM的反应在EV数量或来源方面没有差异。然而,失调的EV相关miRNA的特征存在显著差异,在EAE小鼠中,这些miRNA预计靶向几个与MS相关的生物学过程以及与神经系统、免疫和炎症相关的途径,可能导致疾病恶化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e2d/12267195/624786f34766/fimmu-16-1596935-g007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e2d/12267195/624786f34766/fimmu-16-1596935-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e2d/12267195/bf9cdb17e111/fimmu-16-1596935-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e2d/12267195/ce67cc349840/fimmu-16-1596935-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e2d/12267195/c854c0bd6767/fimmu-16-1596935-g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e2d/12267195/e1cda08793b8/fimmu-16-1596935-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e2d/12267195/dea086756e4d/fimmu-16-1596935-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e2d/12267195/624786f34766/fimmu-16-1596935-g007.jpg

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