Beneficial effect of atorvastatin-modified dendritic cells pulsed with myelin oligodendrocyte glycoprotein autoantigen on experimental autoimmune encephalomyelitis

It is well known that dendritic cells play a key role in producing antigen-specific responses. Inversely, tolerogenic dendritic cells (TolDCs), a specialized subset, induce immune tolerance and negatively regulate autoimmune responses. Statins, the inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase in the mevalonate pathway for cholesterol biosynthesis, might be a promising inductive agent for inducing TolDCs. This study aimed to investigate the effectiveness of TolDCs induced by atorvastatin pulsed with myelin oligodendrocyte glycoprotein 35-55 peptide (MOG35-55) in experimental autoimmune encephalomyelitis mice established by MOG35-55 immunization and to investigate the potential effects on Th17/Treg balance in the murine model of multiple sclerosis. Our results showed that atorvastatin-treated dendritic cells maintained a steady semimature phenotype with a low level of costimulatory molecules and proinflammatory cytokines. Upon an intraperitoneal injection into experimental autoimmune encephalomyelitis mice, TolDCs pulsed with MOG (TolDCs-MOG) significantly alleviated disease activity and regulated Th17/Treg balance with a marked decrease in Th17 cells and an obvious increase in regulatory T cells. Taken together, TolDCs-MOG modified by atorvastatin showed a characteristic tolerogenic phenotype and the antigen-specific TolDCs might represent a new promising strategy for the future treatments for multiple sclerosis.