School of Pharmacy, Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, NO.138 Xianlin Road, 210023 Nanjing, Jiangsu Province, PR China.
Department of Rheumatology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, NO.155 Hanzhong Road, 210029, Nanjing, Jiangsu Province, PR China; The First Clinical Medical College, Nanjing University of Chinese Medicine, NO.138 Xianlin Road, 210023, Nanjing, Jiangsu Province, PR China.
Cell Immunol. 2021 Jul;365:104382. doi: 10.1016/j.cellimm.2021.104382. Epub 2021 May 20.
Rheumatoid arthritis (RA) is a chronic autoimmune disease, and the abnormal differentiation of IL-17-producing T helper (Th17) cells is an important factor in the pathogenesis. Previous studies have shown that microRNAs (miRNAs, miR) act as key regulators of Th17 cells. However, the effects of miRNAs on Th17 cell differentiation and plasticity in RA are not clear. In this study, not only low miR-26b-5p expression and high IL-17A level were observed in the peripheral blood of RA patients, but also the negative correlation between miR-26b-5p and IL-17A was explored. The changes in collagen-induced arthritis (CIA) mice were consistent with those in RA patients. The results of in vitro experiments showed that miR-26b-5p mainly inhibited the initial differentiation of Th17 cells but did not impact the differentiation of induced-Treg into Th17-like cells. Meanwhile, miR-26b-5p mimics treatment alleviated inflammatory responses and reduced Th17 proportion in CIA mice. These results indicated that miR-26b-5p could alleviate the development of mice CIA by inhibiting the excessive Th17 cells, and that miR-26b-5p could modulate the plasticity of Th17 cell differentiation in RA, mainly block the initial differentiation. This may provide a novel strategy for the clinical treatment of RA.
类风湿关节炎（RA）是一种慢性自身免疫性疾病，白细胞介素-17 产生的辅助性 T 细胞（Th17）的异常分化是其发病机制的重要因素。先前的研究表明，微小 RNA（miRNA，miR）作为 Th17 细胞的关键调节因子。然而，miR 对 RA 中 Th17 细胞分化和可塑性的影响尚不清楚。在本研究中，不仅观察到 RA 患者外周血中 miR-26b-5p 表达水平降低，IL-17A 水平升高，而且还探讨了 miR-26b-5p 与 IL-17A 之间的负相关关系。胶原诱导关节炎（CIA）小鼠的变化与 RA 患者的变化一致。体外实验结果表明，miR-26b-5p 主要抑制 Th17 细胞的初始分化，但不影响诱导性 Treg 向 Th17 样细胞的分化。同时，miR-26b-5p 模拟物治疗减轻了 CIA 小鼠的炎症反应，降低了 Th17 比例。这些结果表明，miR-26b-5p 通过抑制过度的 Th17 细胞缓解 CIA 小鼠的发展，并且 miR-26b-5p 可以调节 RA 中 Th17 细胞分化的可塑性，主要阻断初始分化。这可能为 RA 的临床治疗提供新的策略。
