Azizan Amin, Farhadi Elham, Faezi Seyedeh Tahereh, Jamshidi Ahmadreza, Alikhani Majid, Mahmoudi Mahdi
Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Research Center for Chronic Inflammatory Diseases, Tehran University of Medical Sciences, Tehran, Iran.
Immun Inflamm Dis. 2025 Feb;13(2):e70124. doi: 10.1002/iid3.70124.
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by dysregulated immune responses and multi-organ involvement. Dysregulation of apoptosis, a key process for maintaining immune homeostasis, plays a critical role in the pathogenesis of SLE. MicroRNAs (miRNAs), small non-coding RNAs that regulate gene expression, have emerged as important modulators of apoptosis in immune cells, influencing the balance between immune tolerance and autoimmunity.
This review aims to comprehensively summarize recent advancements in understanding the roles of miRNAs in apoptosis regulation within immune cells in SLE, highlighting their therapeutic potential for restoring immune balance and mitigating disease progression.
Aberrant expression of specific miRNAs contributes to the dysregulation of apoptosis in SLE immune cells. Pro-apoptotic miRNAs, such as miR-125b and miR-150, are often downregulated, leading to enhanced survival of autoreactive immune cells. Conversely, anti-apoptotic miRNAs, including miR-21, are upregulated, further disrupting the delicate balance of immune cell apoptosis. Dual-function miRNAs, such as miR-155, exhibit context-dependent roles based on cellular environments and target gene interactions. This dysregulation promotes the persistence of autoreactive immune cells and the development of autoimmunity.
miRNAs play critical roles in modulating apoptosis pathways, making them promising therapeutic targets for SLE. Restoring the balance of pro-apoptotic and anti-apoptotic miRNAs could help reinstate immune tolerance and reduce tissue damage. Future research should focus on elucidating miRNA targetomes, improving delivery systems, and addressing off-target effects to fully harness their therapeutic potential.
系统性红斑狼疮(SLE)是一种慢性自身免疫性疾病,其特征为免疫反应失调和多器官受累。细胞凋亡失调作为维持免疫稳态的关键过程,在SLE的发病机制中起关键作用。微小RNA(miRNA)作为调控基因表达的小型非编码RNA,已成为免疫细胞中细胞凋亡的重要调节因子,影响免疫耐受与自身免疫之间的平衡。
本综述旨在全面总结近期在了解miRNA在SLE免疫细胞凋亡调控中的作用方面取得的进展,突出其在恢复免疫平衡和减轻疾病进展方面的治疗潜力。
特定miRNA的异常表达导致SLE免疫细胞中细胞凋亡失调。促凋亡miRNA,如miR-125b和miR-150,常常下调,导致自身反应性免疫细胞存活增强。相反,抗凋亡miRNA,包括miR-21,上调,进一步破坏免疫细胞凋亡的微妙平衡。双功能miRNA,如miR-155,根据细胞环境和靶基因相互作用发挥依赖于背景的作用。这种失调促进自身反应性免疫细胞的持续存在和自身免疫的发展。
miRNA在调节细胞凋亡途径中起关键作用,使其成为SLE有前景的治疗靶点。恢复促凋亡和抗凋亡miRNA的平衡有助于恢复免疫耐受并减少组织损伤。未来的研究应集中在阐明miRNA靶标组、改进递送系统以及解决脱靶效应,以充分发挥其治疗潜力。