Exosomal non-coding RNAs in autoimmune diseases: molecular mechanisms and potential applications

Autoimmune diseases (ADs) are typically characterized by the immune system erroneously targeting self-organs and tissues, leading to chronic inflammation and organic damage. Current therapeutic strategies, which largely focus on suppressing late-stage inflammation, often fail to achieve satisfactory long-term outcomes. Exosomes, nanoscale extracellular vesicles secreted by diverse cell types, play a pivotal role in intercellular communication and immune regulation through the transfer of bioactive molecules, including non-coding RNAs (ncRNAs). Accumulating evidence indicates that exosomal ncRNAs, primarily microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), have emerged as critical regulators in the pathogenesis of ADs. They modulate key processes such as immune regulation, oxidative stress, autophagy and the cell cycle. In this review, we summarize recent advances in the regulatory mechanisms of exosomal ncRNAs in autoimmune diseases, with specific emphasis on Systemic Lupus Erythematosus (SLE), Rheumatoid Arthritis (RA), Type 1 Diabetes Mellitus (T1DM), Inflammatory Bowel Disease (IBD), and Sjögren's Syndrome (SS). We also highlight their potential as diagnostic biomarkers and therapeutic targets. Finally, we discuss current challenges limiting clinical translation, such as delivery efficiency, stability, immunogenicity and large-scale validation, and propose future directions for the development of precision medicine strategies in autoimmune diseases.