Abstract：
Systemic lupus erythematosus (SLE) is an autoimmune disease associated with an imbalance of T helper 17 (Th17) to regulatory T cells (Tregs). However, the underlying mechanism remains unclear. Increasing evidence suggests that circular RNAs play a crucial role in SLE. Although circETS1 was discovered 30 years ago, detailed exploration of its functions remains limited. In this study, we measured the expression levels of circETS1 in peripheral blood mononuclear cells (PBMCs) and CD4+ T cells of patients with SLE by quantitative polymerase chain reaction. The impact of circETS1 expression on the Th17/Treg balance and underlying mechanism were evaluated using double-luciferase reporter, gain-/loss-of-function, and rescue assays. Receiver operating characteristic (ROC) curve analysis was conducted to assess the diagnostic value of circETS1. Both circETS1 and FOXP3 expression were downregulated in the PBMCs and CD4+ T cells of patients with SLE (n = 28) compared with those in the cells of healthy controls (n = 20). Mechanistically, we found that circETS1 can bind directly to the microRNA miR-1205, acting as a sponge to upregulate the transcription of FOXP3, thereby maintaining the Th17/Treg balance. Notably, ROC analysis showed that the expression level of circETS1 in PBMCs had an area under the curve of 0.873 (95% confidence interval: 0.771-0.976; p < .001) for diagnosing SLE, with a sensitivity of 80.00% and a specificity of 89.29%. Finally, we found negative correlations between the level of circETS1 in PBMCs and disease severity (according to the Systemic Lupus Erythematosus Disease Activity Index) in patients with SLE (r = -0.7712, 95% CI: -0.8910 to -0.5509; p < .001). The imbalance in Th17/Treg cells in SLE may be attributed, in part, to the circETS1/miR-1205/FOXP3 pathway. CircETS1 has potential to serve as a valuable biomarker for the diagnosis and evaluation of SLE.
摘要：
系统性红斑狼疮（SLE）是一种自身免疫性疾病，与辅助性T细胞17（Th17）与调节性T细胞（Tregs）的失衡有关。然而,潜在机制尚不清楚.越来越多的证据表明环状RNA在SLE中起关键作用。虽然circETS1是30年前发现的，对其功能的详细探索仍然有限。在这项研究中,我们通过定量聚合酶链反应检测了SLE患者外周血单个核细胞(PBMC)和CD4+T细胞中circETS1的表达水平.使用双荧光素酶报告基因评估circets1表达对Th17/Treg平衡和潜在机制的影响，功能增益/丧失，和救援试验。进行受试者工作特征（ROC）曲线分析以评估circETS1的诊断价值。与健康对照（n=20）的细胞相比，SLE患者（n=28）的PBMC和CD4T细胞中circETS1和FOXP3表达均下调。机械上,我们发现circETS1可以直接与miR-1205微小RNA结合,作为海绵上调FOXP3的转录,从而维持Th17/Treg平衡.值得注意的是,ROC分析显示PBMC中circETS1的表达水平在诊断SLE的曲线下面积为0.873（95％置信区间：0.771-0.976；p<.001）。敏感性为80.00%，特异性为89.29%。最后,我们发现SLE患者PBMC中circETS1水平与疾病严重程度(根据系统性红斑狼疮疾病活动指数)呈负相关(r=-0.7712,95%CI:-0.8910~-0.509;p<.001).SLE中Th17/Treg细胞的失衡可能归因于在某种程度上,circETS1/miR-1205/FOXP3途径。CircETS1有可能作为诊断和评估SLE的有价值的生物标志物。
