Maresin 1 improves the Treg/Th17 imbalance in rheumatoid arthritis through miR-21
Maresin 1 improves the Treg/Th17 imbalance in rheumatoid arthritis through miR-21
复制标题
Maresin 1 通过 miR-21 改善类风湿关节炎中的 Treg/Th17 失衡
DOI：
10.1136/annrheumdis-2018-213511
复制
发表时间：
2018-11-01
影响因子：
27.4
通讯作者：
Wang, Jianguang
中科院分区：
文献类型：
--
作者：
Jin, Shengwei;Chen, Huaijun;Wang, Jianguang
目的T reg/Th 17失衡在类风湿关节炎（RA）发病中起重要作用。Maresin 1（MaR 1）促进炎症消退并调节免疫反应。本研究旨在探讨MaR 1在RA发病过程中的作用及其与Treg/Th 17平衡的关系。建立胶原诱导性关节炎（CIA）模型，检测临床评分、组织病理学改变及Treg/Th 17比值。纯化的幼稚CD 4 + T细胞用于研究MaR 1对其分化过程的影响，并进行microRNA微阵列研究以研究MaR 1下游microRNA在该过程中的作用。结果与正常对照组相比，活动期RA患者外周血中MaR 1水平明显升高，活动期RA患者外周血中MaR 1水平明显降低。Treg转录因子FoxP 3的表达在活动期RA中最高，在活动期RA中最低，而Th 17转录因子RORc则呈相反趋势。观察到FoxP 3/RORc比率与疾病活动性评分28之间呈负相关。在CIA模型中MaR 1的干预减少了关节炎症和损伤，并改善了失衡的Treg/Th 17比率。在特定的分化条件下，MaR 1可增加Treg细胞比例，降低Th 17细胞比例。结论MaR 1可能通过调节RA患者的Treg/Th 17比例失衡发挥作用，是RA治疗的一个靶点。
Objective T reg/Th17 imbalance plays an important role in rheumatoid arthritis (RA). Maresin 1 (MaR1) prompts inflammation resolution and regulates immune responses. We explored the effect of MaR1 on RA progression and investigated the correlation between MaR1 and Treg/Th17 balance.Methods Both patients with RA and healthy controls were recruited into the study. Collagen-induced arthritis (CIA) model was constructed to detect the clinical score, histopathological changes and Treg/Th17 ratio. Purified naive CD4+ T-cells were used to study the effect of MaR1 on its differentiation process and microRNA microarray studies were performed to investigate MaR1 downstream microRNAs in this process. MicroRNA transfection experiments were conducted by lentivirus to verify the mechanism of MaR1 on Treg/Th17 balance.Results Compared with controls, the MaR1 concentration was higher in the patients with inactive RA and lower in the patients with active RA. Expression of the Treg transcription factor FoxP3 was the highest in inactive RA and the lowest in active RA, while the Th17 transcription factor RORc showed a reverse trend. An inverse correlation was observed between the FoxP3/RORc ratio and Disease Activity Score 28. Intervention of MaR1 in the CIA model reduced joint inflammation and damage, and improved the imbalanced Treg/Th17 ratio. MaR1 increased Treg cells proportion while reduced Th17 cells proportion under specific differentiation conditions. Furthermore, miR-21 was verified as MaR1 downstream microRNA, which was upregulated by MaR1, modulating the Treg/Th17 balance and thus ameliorating the RA progression.Conclusions MaR1 is a therapeutic target for RA, likely operating through effects on the imbalanced Treg/Th17 ratio found in the disease.