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. Correspondence to Yiyun Weng, Department of Neurology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, People's Republic of China Tel: +86 577 55579372; fax: +86 577 55579318; e-mail: wmuwengyiyun@163.com or Correspondence to Xu Zhang, Department of Neurology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, People's Republic of China Tel: +86 577 55579372; fax: +86 577 55579318; e-mail: wmudrzhangxu@163.com Received October 8, 2017 Accepted December 9, 2017 © 2018 Wolters Kluwer Health | Lippincott Williams & Wilkins

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2GHo99g