Immunology Department, School of Medicine, Tehran University of Medical Sciences, Poorsina St, 16 Azar St., Enghelab Ave, Tehran, Iran.
Department of Medical Genetics and Molecular Biology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran.
J Mol Neurosci. 2021 Dec;71(12):2628-2645. doi: 10.1007/s12031-021-01878-8. Epub 2021 Jul 21.
CD4 T cells are known as a noteworthy potential modulator of inflammation in multiple sclerosis (MS). In the current study, we investigated the transcriptome profile of CD4 T cells in patients with relapsing-remitting MS (RRMS) at the relapse phase. We performed RNA sequencing of CD4 T cells isolated from four relapsing-remitting MS (RRMS) patients at the relapse phase and four age- and sex-matched healthy controls. The edgeR statistical method was employed to determine differentially expressed genes (DEGs). Gene set enrichment analysis was subsequently performed. Applying a physical interaction network, genes with higher degrees were selected as hub genes. A total of 1278 and 1034 genes were defined at significantly higher or lower levels, respectively, in CD4 T cells of RRMS patients at the relapse phase as compared with healthy controls. The top up- and downregulated genes were JAML and KDM3A. The detected DEGs were remarkable on chromosomes 1 and 2, respectively. The DEGs were mainly enriched in the pathways "regulation of transcription, DNA-templated," "regulation of B cell receptor signaling pathway," "protein phosphorylation," "epidermal growth factor receptor signaling pathway," and "positive regulation of neurogenesis." Moreover, 16 KEGG pathways mostly associated with the immune system and viral infections were enriched. In the constructed physical interaction networks, UBA52 and TP53 were shown to be the most highly ranked hub genes among upregulated and downregulated genes, respectively. By applying global transcriptome profiling of CD4 T cells, we deciphered the involvement of several novel genes and pathways in MS pathogenesis. The present results must be confirmed by in vivo and in vitro studies.
CD4 T 细胞被认为是多发性硬化症（MS）中炎症的一个显著潜在调节剂。在本研究中，我们在复发缓解型 MS（RRMS）患者的复发期研究了 CD4 T 细胞的转录组谱。我们对 4 例 RRMS 患者在复发期和 4 例年龄和性别匹配的健康对照者的 CD4 T 细胞进行了 RNA 测序。采用 edgeR 统计方法确定差异表达基因（DEGs）。随后进行基因集富集分析。应用物理相互作用网络，选择具有较高度数的基因作为枢纽基因。RRMS 患者在复发期的 CD4 T 细胞中，分别有 1278 个和 1034 个基因被定义为显著上调或下调，与健康对照组相比。上调和下调最显著的基因分别是 JAML 和 KDM3A。检测到的 DEGs 分别在染色体 1 和 2 上显著富集。DEGs 主要富集在“转录调控，DNA 模板”、“B 细胞受体信号通路调控”、“蛋白质磷酸化”、“表皮生长因子受体信号通路”和“神经发生的正调控”等途径中。此外，16 个与免疫系统和病毒感染关系最密切的 KEGG 途径也得到了富集。在构建的物理相互作用网络中，UBA52 和 TP53 分别被显示为上调和下调基因中排名最高的枢纽基因。通过对 CD4 T 细胞进行全基因组转录组谱分析，我们揭示了一些新基因和途径在 MS 发病机制中的参与。这些结果必须通过体内和体外研究来验证。
