Investigate the DNA methylation pattern of T cell cytokines and

advertisement
Investigate the DNA methylation pattern of T cell cytokines
and Programmed cell death-ligand 1 on Antigen presenting
cell in experimental autoimmune encephalomyelitis
Advisor: SHU-FEN WU
Date: 2015/10/02
Student: YONG-LIN CHANG
Abstract
Multiple sclerosis (MS) is a Th1/Th17 CD4+ T cell-mediated chronic
autoimmune disease of the central nervous system. Relapsing-remitting MS
(RRMS) have accounted for the most of the MS. Experimental autoimmune
encephalomyelitis (EAE) is the most commonly animal model using to study of
the MS. In EAE model, immunized with the mixture of mycobacterium and
myelin antigen will activate dendritic cell (DC) to present myelin antigen for T
cell activation. T cells expand and release inflammatory mediators and
cytokines such as IFN-r and IL-17. In recent study, distant T helper lineage has
been shown to involve epigenetic regulation of the differentiation and
polarization. The epigenetic pattern has not been detailed study in EAE model
and MS. Therefore, we aimed to identify the DNA methylation pattern and
disease changes in EAE model .In this study, we induced EAE and observed
the score. It showed that disease progression was correlated with expression
of IFN-r. Then we used pyrosequencing to detect region of IFN-r methylation
pattern. We found that the regions of intron and CNS-6 of IFN-r was
hypo-methylation in EAE mice, while healthy mice were hyper-methylation. On
the other hand, antigen presenting cell played an important role in immune
response. In EAE model, disease progression was regulated by programmed
cell death-ligand 1(PDL1).In primary data of DC, the DNA methylation level of
5-aza-(DNMT inhibitor) or DMSO- treated JAWSâ…ˇ(mice DC cell line) had no
difference at PDL1 by pyrosequencing. In the future, we will compare PDL1
knockout mice to wild type mice in EAE progression and DNA methylation of
different regions of IFN-r and IL-17.
Download