Exosomal miR-23b-3p from bone mesenchymal stem cells alleviates experimental autoimmune encephalomyelitis by inhibiting microglial pyroptosis

Multiple sclerosis (MS) is a chronic autoimmune disease that affects the central nervous system and is marked by inflammation and damage to the myelin sheath surrounding nerve fibers. Recent studies have highlighted the therapeutic value of exosomes (Exos) obtained from bone marrow mesenchymal stem cells (BMSCs) in MS treatment. These BMSC-Exos contain biologically active molecules that show promising results in preclinical evaluations. The aim of this study was to investigate the mechanism of BMSC-Exos containing miR-23b-3p in both LPS-stimulated BV2 microglia and in experimental autoimmune encephalomyelitis (EAE), an animal model for MS. Exos were isolated from BMSCs, and their effects were evaluated in vitro by co-culturing with BV2 microglia. The interaction between miR-23b-3p and its downstream targets was also explored. The efficacy of BMSC-Exos was further verified in vivo by injecting the Exos into EAE mice. The results showed that BMSC-Exos containing miR-23b-3p reduced microglial pyroptosis in vivo by specifically binding to and suppressing the expression of NEK7. In vivo, BMSC-Exos containing miR-23b-3p alleviated the severity of EAE by decreasing microglial inflammation and pyroptosis via the repression of NEK7. These findings provide new insights into the therapeutic potential of BMSC-Exos containing miR-23b-3p for MS. •Exosomal miR-23b-3p from bone mesenchymal stem cells alleviates EAE.•miR-23b-3p reduces microglial pyroptosis both in vitro and in vivo.•miR-23b-3p specifically suppresses NEK7 expression.•BMSC-Exos containing miR-23b-3p relieves the severity of EAE.•Alleviation of EAE reduces microglial inflammation and pyroptosis through the reduction of NEK7 expression.