Immune cell-derived extracellular vesicular microRNAs induce pancreatic beta cell apoptosis.

Background: Type 1 diabetes mellitus (T1DM) is an autoimmune disease caused by an autoimmune response against pancreatic islet β cells. Increasing evidence indicates that specific microRNAs (miRNAs) from immune cells extracellular vesicles are involved in islet β cells apoptosis. Methods: In this study, the microarray datasets GSE27997 and GSE137637 were downloaded from the Gene Expression Omnibus (GEO) database. miRNAs that promote islet β cells apoptosis in T1DM were searched in PubMed. We used the FunRich tool to determine the miRNA expression in extracellular vesicles derived from immune cells associated with islet β cell apoptosis, of which we selected candidate miRNAs based on fold change expression. Potential upstream transcription factors and downstream target genes of candidate miRNAs were predicted using TransmiR V2.0 and starBase database, respectively. Results: Candidate miRNAs expressed in extracellular vesicles derived from T cells, pro-inflammatory macrophages, B cells, and dendritic cells were analyzed to identify the miRNAs involved in β cells apoptosis. Based on these candidate miRNAs, 25 downstream candidate genes, which positively regulate β cell functions, were predicted and screened; 17 transcription factors that positively regulate the candidate miRNAs were also identified. Conclusions: Our study demonstrated that immune cell-derived extracellular vesicular miRNAs could promote islet β cell dysfunction and apoptosis. Based on these findings, we have constructed a transcription factor-miRNA-gene regulatory network, which provides a theoretical basis for clinical management of T1DM. This study provides novel insights into the mechanism underlying immune cell-derived extracellular vesicle-mediated islet β cell apoptosis.