Genome-wide DNA methylation profiling identifies epigenetic changes in CD4+ and CD14+ cells of multiple sclerosis patients.
Genome-wide DNA methylation profiling identifies epigenetic changes in CD4+ and CD14+ cells of multiple sclerosis patients.
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DOI：
10.1016/j.msard.2022.103714
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发表时间：
2022-02
影响因子：
4
通讯作者：
I. Kiselev;Ludmila V. Danilova;N. Baulina;O. Baturina;Marsel R Kabilov;A. Boyko;O. Kulakova;O. Favorova
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文献类型：
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作者：
I. Kiselev;Ludmila V. Danilova;N. Baulina;O. Baturina;Marsel R Kabilov;A. Boyko;O. Kulakova;O. Favorova
多发性硬化症（MS）是一种慢性自身免疫性和中枢神经系统退行性疾病，其在暴露于环境影响后在遗传易感个体中发展。MS的环境触发因素，如病毒感染或吸烟，被证明会影响DNA甲基化，从而使这种重要的表观遗传机制参与病理过程的发展。为了鉴定MS相关的DNA甲基化标志，我们使用Illumina 450 K甲基化阵列对从相同的未经治疗的复发缓解型MS患者和健康受试者收集的两个细胞群体（CD 4 + T淋巴细胞和CD 14+单核细胞）进行了全基因组DNA甲基化分析。我们揭示了MS中两种细胞群体的DNA甲基化的显著变化。在MS患者的CD 4+细胞中，大多数差异甲基化位置（DMPs）显示为低甲基化，而在CD 14+细胞中为高甲基化。CD 4+和CD 14+细胞中HLA-DRB 1基因甲基化差异与DRB 1 *15等位基因携带相关，与疾病状态无关。此外，约20%的DMPs在两个细胞群体之间共享，并且具有相同的甲基化变化方向;它们可能参与MS中发生的基本表观遗传过程。这些发现表明，免疫细胞中DNA甲基化的表观遗传机制有助于MS;现在需要进一步的研究来验证这些结果并了解其功能意义。
Multiple sclerosis (MS) is a chronic autoimmune and degenerative disease of the central nervous system, which develops in genetically predisposed individuals upon exposure to environmental influences. Environmental triggers of MS, such as viral infections or smoking, were demonstrated to affect DNA methylation, and thus to involve this important epigenetic mechanism in the development of pathological process. To identify MS-associated DNA methylation hallmarks, we performed genome-wide DNA methylation profiling of two cell populations (CD4+ T-lymphocytes and CD14+ monocytes), collected from the same treatment-naive relapsing-remitting MS patients and healthy subjects, using Illumina 450 K methylation arrays. We revealed significant changes in DNA methylation for both cell populations in MS. In CD4+ cells of MS patients the majority of differentially methylated positions (DMPs) were shown to be hypomethylated, while in CD14+ cells – hypermethylated. Differential methylation of HLA-DRB1gene in CD4+ and CD14+ cells was associated with carriage ofDRB1*15 allele independently from the disease status. Besides, about 20% of identified DMPs were shared between two cell populations and had the same direction of methylation changes; they may be involved in basic epigenetic processes occuring in MS. These findings suggest that the epigenetic mechanism of DNA methylation in immune cells contributes to MS; further studies are now required to validate these results and understand their functional significance.