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支气管肺泡细胞甲基组和转录组特征与多发性硬化症患者吸烟的关系。

Methylome and transcriptome signature of bronchoalveolar cells from multiple sclerosis patients in relation to smoking.

机构信息

Department of Clinical Neuroscience and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.

Department of Medicine, Solna and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.

出版信息

Mult Scler. 2021 Jun;27(7):1014-1026. doi: 10.1177/1352458520943768. Epub 2020 Jul 30.

DOI:10.1177/1352458520943768
PMID:32729352
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8145441/
Abstract

BACKGROUND

Despite compelling evidence that cigarette smoking impacts the risk of developing multiple sclerosis (MS), little is known about smoking-associated changes in the primary exposed lung cells of patients.

OBJECTIVES

We aimed to examine molecular changes occurring in bronchoalveolar lavage (BAL) cells from MS patients in relation to smoking and in comparison to healthy controls (HCs).

METHODS

We profiled DNA methylation in BAL cells from female MS ( = 17) and HC ( = 22) individuals, using Illumina Infinium EPIC and performed RNA-sequencing in non-smokers.

RESULTS

The most prominent changes were found in relation to smoking, with 1376 CpG sites (adjusted  < 0.05) differing between MS smokers and non-smokers. Approximately 30% of the affected genes overlapped with smoking-associated changes in HC, leading to a strong common smoking signature in both MS and HC after gene ontology analysis. Smoking in MS patients resulted in additional discrete changes related to neuronal processes. Methylome and transcriptome analyses in non-smokers suggest that BAL cells from MS patients display very subtle (not reaching adjusted  < 0.05) but concordant changes in genes connected to reduced transcriptional/translational processes and enhanced cellular motility.

CONCLUSIONS

Our study provides insights into the impact of smoking on lung inflammation and immunopathogenesis of MS.

摘要

背景

尽管有确凿的证据表明吸烟会影响多发性硬化症（MS）的发病风险，但对于吸烟与患者肺部初级暴露细胞相关的变化知之甚少。

目的

我们旨在研究与吸烟有关的 MS 患者支气管肺泡灌洗液（BAL）细胞中发生的分子变化，并与健康对照（HC）进行比较。

方法

我们使用 Illumina Infinium EPIC 对来自女性 MS（n=17）和 HC（n=22）个体的 BAL 细胞进行 DNA 甲基化分析，并在不吸烟的个体中进行 RNA 测序。

结果

最显著的变化与吸烟有关，MS 吸烟者与非吸烟者之间有 1376 个 CpG 位点（调整后 < 0.05）存在差异。受影响基因的约 30%与 HC 中的吸烟相关变化重叠，导致在基因本体分析后，MS 和 HC 中均存在强烈的共同吸烟特征。MS 患者吸烟会导致与神经元过程相关的额外离散变化。非吸烟者的甲基组和转录组分析表明，MS 患者的 BAL 细胞显示出非常细微（未达到调整后 < 0.05）但一致的变化，这些变化与降低的转录/翻译过程和增强的细胞迁移有关。

结论

我们的研究提供了关于吸烟对肺部炎症和 MS 免疫发病机制影响的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b918/8145441/f6feaf522c26/10.1177_1352458520943768-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b918/8145441/411f23984819/10.1177_1352458520943768-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b918/8145441/d71b1631b5c8/10.1177_1352458520943768-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b918/8145441/266ec1b5976d/10.1177_1352458520943768-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b918/8145441/f6feaf522c26/10.1177_1352458520943768-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b918/8145441/411f23984819/10.1177_1352458520943768-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b918/8145441/d71b1631b5c8/10.1177_1352458520943768-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b918/8145441/266ec1b5976d/10.1177_1352458520943768-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b918/8145441/f6feaf522c26/10.1177_1352458520943768-fig4.jpg

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