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

• Published in: Neuroreport Vol. 29; no. 4; p. 317
• Main Authors: Chen, Zhibo, Yang, Dehao, Peng, Xiao, Lin, Jie, Su, Zhongqian, Li, Jia, Zhang, Xu, Weng, Yiyun
• Format: Journal Article
• Language: English
• Published: England 07.03.2018
• Subjects: Animals; Atorvastatin - pharmacology; Autoantigens - metabolism; Cell Movement; Cytokines - blood; Dendritic Cells - drug effects; Dendritic Cells - immunology; Dendritic Cells - pathology; Encephalomyelitis, Autoimmune, Experimental - drug therapy; Encephalomyelitis, Autoimmune, Experimental - immunology; Encephalomyelitis, Autoimmune, Experimental - pathology; Female; Immunologic Factors - pharmacology; Mice, Inbred C57BL; Multiple Sclerosis - drug therapy; Multiple Sclerosis - immunology; Multiple Sclerosis - pathology; Myelin-Oligodendrocyte Glycoprotein - immunology; Spinal Cord - drug effects; Spinal Cord - immunology; Spinal Cord - pathology; Spleen - drug effects; Spleen - immunology; Spleen - pathology; T-Lymphocytes, Regulatory - drug effects; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - pathology
• ISSN: 1473-558X
• DOI: 10.1097/WNR.0000000000000962

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.