BMSCs-derived exosome miR-29a-3p improved the stability of rat myasthenia gravis by regulating Treg/Th17 cells 

Abstract

Myasthenia gravis (MG) is an autoimmune disorder mediated by antibodies targeting the acetylcholine receptor. Exosomal-derived miRNAs have been implicated in immune modulation and the pathogenesis of autoimmune diseases. However, the expression and functional role of exosomal miR-29a-3p in MG remains poorly understood. This study aimed to investigate the therapeutic effect and mechanism of miR-29a-3p derived from stem cell exosomes (Exos) on experimental autoimmune myasthenia gravis (EAMG) rats. EAMG was induced in rats by injection of the subunit of the rat nicotinic anti-acetylcholine receptor (AChR) R97-116 peptide. In addition to the control group, EAMG rats were randomly allocated into the following groups: EAMG model group, Exo group, Exo-NC-agomir group, and Exo- miR-29a-3p-agomir group. Our results found that BMSCs-Exo promoted miR-29a-3p expression in gastrocnemius of EAMG rats. Bone marrow mesenchymal stem cells (BMSCs) derived exosome miR-29a-3p improved the hanging ability and swimming time of EMGA rats and weakened the degree of muscle fiber atrophy. Furthermore, exosomes from miR-29a-3p overexpressing BMSCs reduced the content of AchR-Ab in the serum of EAMG rats. BMSC-derived exosome miR-29a-3p further suppressed the expression of IFN-γ and enhanced the expression of IL-4 and IL-10 in the serum of EAMG rats by restoring the Th17/Treg cells balance. Therefore, BMSCs-derived exosome miR-29a-3p improved the stability of rat myasthenia gravis by regulating Treg/Th17 cells. It may be an effective treatment for MG.