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

Abstract:

: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.

journal_name

Neuroreport

journal_title

Neuroreport

authors

Chen Z,Yang D,Peng X,Lin J,Su Z,Li J,Zhang X,Weng Y

doi

10.1097/WNR.0000000000000962

subject

Has Abstract

pub_date

2018-03-07 00:00:00

pages

317-327

issue

4

eissn

0959-4965

issn

1473-558X

journal_volume

29

pub_type

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