Biochemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Biochemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Life Sci. 2022 Nov 15;309:120965. doi: 10.1016/j.lfs.2022.120965. Epub 2022 Sep 22.
Behçet's disease (BD) and systemic lupus erythematosus (SLE) are two autoimmune inflammatory diseases of indefinite etiology. However, up till now, no study has explored the exact regulatory mechanisms of lncRNA maternally expressed gene-3 (MEG3) over the balance between regulatory T-cells (Treg) and T helper-17 (Th17) cells in BD and SLE.
The current study aimed to investigate the role of lncRNA MEG3 in the interplay between the anti-inflammatory Treg/transcription factor forkhead box P3 (FOXP3) axis versus the pro-inflammatory Th17/retinoic acid orphan receptor-γt (RORγt) axis.
100 subjects, 35 with BD and 35 with SLE in addition to 30 healthy participants were included in the study. Gene expression analysis was performed and ShinyGO database was utilized for in-depth analysis and graphical visualization of the gene ontology (GO) and pathway enrichment analysis for lncRNA and the other target genes.
The current results demonstrate the upregulation of lncRNA MEG3 in BD but not SLE patients. Moreover, significant differences in RORγt and FOXP3 were found between BD and SLE patients. The present findings linked lncRNA MEG3 to BD activity scores as well as CRP levels. Finally, lncRNA MEG3 showed excellent diagnostic power for BD, in addition to adequate discriminative power that can be used to differentiate between BD and SLE.
The current study objectively elucidated a framework for the involvement of Treg/Th17 through transcription factors RORγt and FOXP3, in addition to their links to the downstream cytokines network including TGF-ꞵ, IL-10, IL-17 and IL-23 in BD and SLE pathogenesis and activity.
贝赫切特病（BD）和系统性红斑狼疮（SLE）是两种病因不明的自身免疫性炎症性疾病。然而，到目前为止，还没有研究探讨长链非编码 RNA 母源表达基因 3（MEG3）在 BD 和 SLE 中调节性 T 细胞（Treg）和辅助性 T 细胞 17（Th17）细胞之间平衡的确切调控机制。
本研究旨在探讨长链非编码 RNA MEG3 在抗炎性 Treg/叉头框 P3（FOXP3）轴与促炎性 Th17/维甲酸孤儿受体-γt（RORγt）轴之间相互作用中的作用。
纳入 100 例患者，其中 35 例为 BD 患者，35 例为 SLE 患者，30 例健康对照者。进行基因表达分析，并利用 ShinyGO 数据库对 lncRNA 和其他靶基因的基因本体（GO）和通路富集分析进行深入分析和图形可视化。
本研究结果表明，BD 患者中长链非编码 RNA MEG3 表达上调，但 SLE 患者中未上调。此外，BD 和 SLE 患者之间 RORγt 和 FOXP3 存在显著差异。本研究结果将 lncRNA MEG3 与 BD 活动评分以及 CRP 水平联系起来。最后，lncRNA MEG3 对 BD 具有良好的诊断能力，且具有足够的鉴别能力，可用于区分 BD 和 SLE。
本研究客观地阐明了 Treg/Th17 通过转录因子 RORγt 和 FOXP3 及其与下游细胞因子网络（包括 TGF-ꞵ、IL-10、IL-17 和 IL-23）的联系，在 BD 和 SLE 发病机制和活动中的作用框架。
