Methylome and transcriptome signature of bronchoalveolar cells from multiple sclerosis patients in relation to smoking.
Methylome and transcriptome signature of bronchoalveolar cells from multiple sclerosis patients in relation to smoking.
复制标题
多发性硬化症患者支气管肺泡细胞的甲基组和转录组特征与吸烟的关系。
DOI：
10.1177/1352458520943768
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发表时间：
2021-06
期刊：
影响因子：
--
通讯作者：
Kular L
中科院分区：
文献类型：
--
作者：
Ringh MV;Hagemann-Jensen M;Needhamsen M;Kullberg S;Wahlström J;Grunewald J;Brynedal B;Jagodic M;Ekström TJ;Öckinger J;Kular L
尽管有令人信服的证据表明吸烟会影响多发性硬化症（MS）的发病风险，但人们对吸烟相关的患者原发性暴露肺细胞的变化知之甚少。我们的目的是研究发生在MS患者的支气管肺泡灌洗（BAL）细胞的分子变化与吸烟和健康对照（HC）相比。我们使用Illumina Infinium EPIC分析了来自女性MS（n = 17）和HC（n = 22）个体的BAL细胞中的DNA甲基化，并在非吸烟者中进行了RNA测序。最显著的变化与吸烟有关，MS吸烟者和非吸烟者之间有1376个CpG位点（校正P < 0.05）不同。大约30%的受影响的基因与HC中吸烟相关的变化重叠，导致基因本体分析后MS和HC中具有强烈的共同吸烟特征。MS患者吸烟导致与神经元过程相关的额外离散变化。在非吸烟者中的甲基化组和转录组分析表明，来自MS患者的BAL细胞在与减少的转录/翻译过程和增强的细胞运动性相关的基因中显示出非常细微（未达到校正的P < 0.05）但一致的变化。我们的研究为吸烟对肺部炎症和MS免疫发病机制的影响提供了见解。
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. 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). We profiled DNA methylation in BAL cells from female MS (n = 17) and HC (n = 22) individuals, using Illumina Infinium EPIC and performed RNA-sequencing in non-smokers. The most prominent changes were found in relation to smoking, with 1376 CpG sites (adjusted P < 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 P < 0.05) but concordant changes in genes connected to reduced transcriptional/translational processes and enhanced cellular motility. Our study provides insights into the impact of smoking on lung inflammation and immunopathogenesis of MS.
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影响因子：
6.8
作者：
Corley, Janie;Cox, Simon R.;Deary, Ian J.
通讯作者：
Deary, Ian J.
DOI：
10.1165/rcmb.2003-0177oc
发表时间：
2004-02-01
影响因子：
6.4
作者：
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作者：
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3.8
作者：
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通讯作者：
Shibutani, Makoto
影响因子：
3.5
作者：
Shenker, Natalie S.;Polidoro, Silvia;Flanagan, James M.
通讯作者：
Flanagan, James M.