Multi-Omics Analysis in Autoimmunity: Identification of MicroRNA Regulatory Networks and Cell-Type-Specific...

Autoimmune diseases (AIDs) arise from complex immune dysregulations involving multiple immune cell types, cytokines, and molecular mediators. Among these, microRNAs (miRNAs) have recently emerged as key regulators of leukocyte processes and are frequently dysregulated in AIDs. However, their role in disease pathophysiology remains poorly understood. In this study, we performed a comprehensive analysis of miRNA expression in three immune populations, namely, CD14⁺ monocytes, neutrophils, and CD8⁺ T cells, in multiple sclerosis (MS) and type 1 diabetes (T1D), two prototypical AIDs. Our results reveal distinct patterns of miRNA dysregulation in each cell type, with monocytes from T1D patients showing enhanced M1 polarization and supporting inflammatory vascular damage. On the other hand, CD8⁺ T cells from MS patients show profound alterations related to CD8⁺ T cell-fate commitment, apoptosis regulation, and migratory capacity. Notably, we identified miRNAs that regulate key transcription factors such as FOXP3, IRF4, and RORγt, potentially shaping T cell differentiation programs. Our results suggest that miRNA networks play a central role in orchestrating disease-specific dysregulation in AIDs. By elucidating these intricate regulatory mechanisms, our study provides a foundation for future therapeutic strategies targeting miRNAs in autoimmunity.