| Summary: | 碩士 === 國立中正大學 === 生物醫學研究所 === 99 === Regulatory T (Treg) cells play an indispensable role in immune tolerance and suppress immune responses after the infection and expressing an important transcription factor Forkhead box P3 (FOXP3). FOXP3 plays important roles for the development and function of Treg cells and has been identified as a specific marker for Treg cells. Autoimmune diseases arise from an overactive immune response against tissues normally present in the body. As previous studies shown, patients that suffered from autoimmune diseases have lower percentage of regulatory T cells including multiple scelrosis. Previous studies have indicated that epigenetic modifications were involved in the regulation of FOXP3 expression; treatment with the DNA demethylation agent enhanced the Treg-mediated suppression and decreased the occurrence of diabetes in NOD mice. In our study, we investigated the treatment of DNA demethylation agent 5-Aza (5-Aza-2- deoxycytidine) in experimental allergic encephalomyelitis (EAE), a widely used animal model for studying human multiple sclerosis, to evaluate the demethylation effect in autoimmune therapy. Using GFP knock-in FOXP3 transgenic mice to evaluate the FOXP3 expression after 5-Aza treatment, 5-Aza treatment increased the GFP expression in CD4+CD25- T cells in vitro and in vivo. Furthermore, MOG-induced mouse pretreated with 5-Aza delayed the onset of EAE at least about 20 days, and, in most cases, there is not any EAE clinical symptom. Moreover, the 5-Aza pretreated mice seem to have no inflammatory responses in central nervous system, because of the very low RNA expression level of inflammatory cytokines could be detected in central nervous system. Therefore, we hypothesized that pretreatment with 5-Aza in vivo enhanced the Treg-mediated suppression and could provide a protective effect against pathogenic lymphocyte, and as a result, decreased the occurrence of experimental allergic encephalomyelitis.
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