Tan Shuting, Liu Jingli, Chen Liuling, Li Ruying, Li Jinpin
Department of Neurology, the First Affifiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning 530021, PR China.
Department of Neurology, the First Affifiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning 530021, PR China.
Immunol Lett. 2025 Dec;276:107050. doi: 10.1016/j.imlet.2025.107050. Epub 2025 Jun 7.
MicroRNAs are a class of endogenous noncoding small RNAs. miR-125a-5p is involved in immunoregulatory mechanisms in autoimmune diseases. Myasthenia gravis (MG) is an autoimmune disease in which regulatory T cells (Tregs) exhibit reduced numbers and functional defects, with decreased expression of the Treg cell-specific transcription factor Foxp3. Our previous study identified an abnormally high expression of miR-125a-5p in thymoma-associated myasthenia gravis, however, the involvement of miR-125a-5p in the pathogenesis of myasthenia gravis in vivo is unclear. In this study, we explored the role of thymic miR-125a-5p abnormalities in the pathogenesis of myasthenia gravis by establishing an experimental autoimmune myasthenia gravis model. Muscle strength score, low-frequency repetitive nerve stimulation, and serum acetylcholine receptor antibody were performed. The relative expression of miR-125a-5p and Foxp3 in the thymus and spleen was quantified, and the percentage of Treg cells, the levels of the inhibitory cytokines IL-10 and TGF-β1, and the proliferative capacity of splenic T lymphocytes were detected. Our findings revealed significant upregulation of miR-125a-5p expression in myasthenia gravis models. Reducing miR-125a-5p levels alleviated muscle weakness symptoms, elevated Foxp3 expression, enhanced the number of Treg cells, elevated the levels of the Treg-associated inhibitory cytokines IL-10 and TGF-β1, and inhibited the proliferative function of splenic T lymphocytes. The opposite result was obtained when miR-125a-5p was overexpressed. These results suggest that miR-125a-5p can inhibit Foxp3 expression, leading to a decrease in the number and abnormal function of Treg cells. Thus, our findings suggest that miR-125a-5p participates in the pathogenesis of myasthenia gravis by targeting Foxp3 to regulate the function of Treg cells, providing new insights to explore the immunoregulatory mechanisms of miR-125a-5p in myasthenia gravis.
微小RNA是一类内源性非编码小RNA。miR-125a-5p参与自身免疫性疾病的免疫调节机制。重症肌无力（MG）是一种自身免疫性疾病，其中调节性T细胞（Tregs）数量减少且功能缺陷，Treg细胞特异性转录因子Foxp3的表达降低。我们之前的研究发现miR-125a-5p在胸腺瘤相关性重症肌无力中异常高表达，然而，miR-125a-5p在重症肌无力发病机制中的体内作用尚不清楚。在本研究中，我们通过建立实验性自身免疫性重症肌无力模型，探讨胸腺miR-125a-5p异常在重症肌无力发病机制中的作用。进行了肌肉力量评分、低频重复神经刺激和血清乙酰胆碱受体抗体检测。定量分析了胸腺和脾脏中miR-125a-5p和Foxp3的相对表达，并检测了Treg细胞的百分比、抑制性细胞因子IL-10和TGF-β1的水平以及脾T淋巴细胞的增殖能力。我们的研究结果显示重症肌无力模型中miR-125a-5p表达显著上调。降低miR-125a-5p水平可缓解肌无力症状，提高Foxp3表达，增加Treg细胞数量，提高Treg相关抑制性细胞因子IL-10和TGF-β1的水平，并抑制脾T淋巴细胞的增殖功能。当miR-125a-5p过表达时，得到相反的结果。这些结果表明，miR-125a-5p可抑制Foxp3表达，导致Treg细胞数量减少和功能异常。因此，我们的研究结果表明，miR-125a-5p通过靶向Foxp3调节Treg细胞功能参与重症肌无力的发病机制，为探索miR-125a-5p在重症肌无力中的免疫调节机制提供了新的见解。
