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微小 RNA let-7g-5p 通过抑制 Th17 细胞分化缓解鼠胶原诱导性关节炎。

MicroRNA let-7g-5p alleviates murine collagen-induced arthritis by inhibiting Th17 cell differentiation.

机构信息

Jiangsu Provincial Key Laboratory of Pharmacology and Safety Evaluation of Material Medical, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, PR China.

The First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210023, PR China.

出版信息

Biochem Pharmacol. 2020 Apr;174:113822. doi: 10.1016/j.bcp.2020.113822. Epub 2020 Jan 25.

Abstract

Rheumatoid arthritis (RA) is a chronic and systemic autoimmune disease with complicated pathogenesis. IL-17-producing T helper cells (Th17) are important players in the RA process. Despite numerous researches have proven that microRNAs (miRNAs) are crucial to regulate autoimmune diseases including RA, the effect of miRNAs on Th17 cell differentiation and function in the RA progress is not clear. Here, our results showed that the expression of miRNA let-7g-5p was substantially lower in RA patients and CIA mice compared with healthy controls, accompanied by the increased Th17 cell population. Furthermore, the inhibition of let-7g-5p on Th17 cell differentiation and function were verified in vitro. Notably, the disease severity in CIA mice was significantly alleviated after the treatment of let-7g-5p mimics. In addition, let-7g-5p mimics treatment markedly down-regulated the frequency of Th17 cells in CIA mice. Taken together, our findings indicate that let-7g-5p can ameliorate CIA through blocking the differentiation of Th17 cells, which may be a novel strategy to treat autoimmune diseases such as RA.

摘要

类风湿关节炎(RA)是一种慢性、全身性自身免疫性疾病,其发病机制复杂。白细胞介素 17 产生的辅助性 T 细胞(Th17)是 RA 发病过程中的重要参与者。尽管大量研究已经证明微小 RNA(miRNA)对于包括 RA 在内的自身免疫性疾病的调控至关重要,但 miRNA 对 RA 进展中 Th17 细胞分化和功能的影响尚不清楚。在这里,我们的结果表明,与健康对照组相比,RA 患者和 CIA 小鼠中 miRNA let-7g-5p 的表达显著降低,同时 Th17 细胞群体增加。此外,在体外验证了 let-7g-5p 对 Th17 细胞分化和功能的抑制作用。值得注意的是,在 CIA 小鼠中,let-7g-5p 模拟物治疗后疾病严重程度显著减轻。此外,let-7g-5p 模拟物治疗明显降低了 CIA 小鼠中 Th17 细胞的频率。总之,我们的研究结果表明,let-7g-5p 可以通过阻断 Th17 细胞的分化来改善 CIA,这可能是治疗 RA 等自身免疫性疾病的一种新策略。

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