The Role of MicroRNAs in Treg-Derived Extracellular Vesicles: A Narrative Review Focusing on Immune-Related Diseases

Regulatory T cells (Tregs) are a unique class of immunosuppressive cells that play a key role in managing immune-related diseases. Growing evidence indicates that the immunosuppressive effects of Tregs also rely on cell-to-cell interactions that are facilitated by the secretion of extracellular vesicles (EVs). Treg-derived EVs (Treg-EVs) are lipid bilayer vesicles that are released from Tregs and have been shown to promote intercellular communication and facilitate immune regulation by transferring various messenger RNAs (mRNAs), microRNAs (miRNAs), and proteins. miRNAs are small, noncoding RNA molecules that regulate gene expression after transcription and can influence multiple target genes by binding to the 3'-untranslated region (UTR) of target mRNAs to exert influence on a wide array of cellular functions. Although the roles of miRNAs and Treg-EVs in various diseases have been extensively studied, the regulatory functions of the different miRNAs within Treg-EVs in immune-related diseases remain largely unexplored. In this narrative review, we investigate the functional roles of Tregs and their derived EVs in immune regulation. Then, we discuss the specific roles of miRNAs within Treg-EVs in the context of rheumatoid arthritis (RA), inflammatory bowel disease (IBD), autoimmune vasculitis, multiple sclerosis (MS), and kidney and skin allografts by investigating recent research in autoimmune diseases and transplantation. In these situations, different Treg-EVs can support the treatment of immune-related conditions by delivering miRNAs to specific immune cells and promoting immunosuppression through multiple mechanisms.