miR-20b-5p exerts protective effects against experimental autoimmune encephalomyelitis in mice by inhibiting NLRP3 transcription and NLRP3/ASC/caspase-1 axis activation

BackgroundExperimental autoimmune encephalomyelitis (EAE) is a fatal autoimmune disease, and microRNAs (miRNAs) play vital roles in regulating immune responses.ObjectivesThis study aimed to explore the effect of miR-20b-5p in mice with EAE as well as the underlying mechanism.MethodsAn EAE mouse model was established via myelin oligodendrocyte glycoprotein (MOG)35-55 peptide induction, and miR-20b-5p expression was measured. Then, miR-20b-5p agomiR was injected via the caudal vein. Clinical score evaluation, body weight measurement, and histological staining were performed, and lactic dehydrogenase (LDH), superoxide dismutase (SOD), catalase (CAT) and reactive oxygen species (ROS) levels were measured. The binding of miR-20b-5p to Nod-like receptor protein 3 (NLRP3) was analysed by dual-luciferase assay. Levels of NLRP3, ASC and caspase-1 were measured. The effect of NLRP3 on EAE model mice was analysed via rescue experiments.ResultsThe clinical scores and body weight of EAE model mice were reduced, and tissue damage was exacerbated. miR-20b-5p was expressed at low levels in EAE model mice, and their symptoms were ameliorated after miR-20b-5p overexpression. Moreover, miR-20b-5p overexpression alleviated pyroptosis, inflammation and oxidative stress in the spinal cord tissues of EAE model mice. Mechanistically, miR-20b-5p targeted NLRP3 transcription and inhibited NLRP3/ASC/caspase-1 pathway activation. NLRP3 overexpression activated the NLRP3/ASC/caspase-1 pathway and abolished the protective effect of miR-20b-5p on EAE.ConclusionmiR-20b-5p exerted a protective effect on EAE in mice by inhibiting NLRP3 transcription and NLRP3/ASC/caspase-1 pathway activation.