Role of Mirnas in Apoptosis Pathways of Immune Cells in Systemic Lupus Erythematosus Publisher Pubmed



Azizan A^{1, 2} ; Farhadi E^{1, 2} ; Faezi ST¹ ; Jamshidi A¹ ; Alikhani M¹ ; Mahmoudi M^{1, 2} Show Affiliations
Source: Immunity, Inflammation and Disease Published:2025

Abstract

Background: 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. Objectives: 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. Results: 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. Conclusions: 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. © 2025 The Author(s). Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.