School of Pharmacy, Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China.
Department of Rheumatology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.
J Clin Lab Anal. 2023 Mar;37(5):e24845. doi: 10.1002/jcla.24845. Epub 2023 Mar 1.
Rheumatoid arthritis (RA) is a persistent and systemic autoimmunity disease. The abnormal differentiation of Treg cells is important in pathogenesis. Despite previous studies showed that microRNAs (miRNAs, miR) are pivotal modulators of Treg cells, the effect of miRNAs on Treg cell differentiation and function is not clear. Our study wants to reveal the relationship of miR-143-3p with the differentiative ability and biofunction of Treg cells during the development of RA.
The Expressing level of miR-143-3p and cell factor generation in peripheral blood (PB) of RA sufferers were identified by ELISA or RT-qPCR. The roles of miR-143-3p in Treg cell differentiation were studied via ShRNA/lentivirus transfection. Male DBA/1 J mice were separated into control, model, control mimics, and miR-143-3p mimics groups to analyze the anti-arthritis efficacy, the differentiative ability of Treg cells, and the expression level of miR-143-3p.
Our team discovered that the Expressing level of miR-143-3p was related to RA disease activities in a negative manner, and remarkably related to antiinflammation cell factor IL-10. In vitro, the expression of miR-143-3p in the CD4 T cells upregulated the percentage of CD4 CD25 Fxop3 cells (Tregs) and forkhead box protein 3 (Foxp3) mRNA expression. Evidently, miR-143-3p mimic intervention considerably upregulated the content of Treg cells in vivo, validly avoided CIA progression, and remarkably suppressed the inflammatory events of joints in mice.
Our findings indicated that miR-143-3p could ameliorate CIA through polarizing naive CD4 T cells into Treg cells, which may be a novel strategy to treat autoimmune diseases such as RA.
类风湿关节炎（RA）是一种持续且系统性的自身免疫性疾病。调节性 T 细胞（Treg 细胞）的异常分化在发病机制中很重要。尽管先前的研究表明 microRNAs（miRNAs，miR）是 Treg 细胞的关键调节因子，但 miRNAs 对 Treg 细胞分化和功能的影响尚不清楚。我们的研究旨在揭示 miR-143-3p 与 RA 发展过程中 Treg 细胞分化能力和生物功能的关系。
通过 ELISA 或 RT-qPCR 鉴定 RA 患者外周血（PB）中 miR-143-3p 的表达水平和细胞因子生成。通过 ShRNA/慢病毒转染研究 miR-143-3p 在 Treg 细胞分化中的作用。将雄性 DBA/1J 小鼠分为对照组、模型组、对照模拟物组和 miR-143-3p 模拟物组，以分析抗关节炎疗效、Treg 细胞的分化能力以及 miR-143-3p 的表达水平。
我们发现 miR-143-3p 的表达水平与 RA 疾病活动呈负相关，与抗炎细胞因子 IL-10 显著相关。体外，CD4 T 细胞中 miR-143-3p 的表达上调了 CD4 CD25 Fxop3 细胞（Treg）和叉头框蛋白 3（Foxp3）mRNA 的表达百分比。显然，miR-143-3p 模拟物干预显著上调了体内 Treg 细胞的含量，有效地避免了 CIA 的进展，并显著抑制了小鼠关节的炎症事件。
我们的研究结果表明，miR-143-3p 可通过将幼稚 CD4 T 细胞极化为 Treg 细胞来改善 CIA，这可能是治疗 RA 等自身免疫性疾病的新策略。
