The modulatory mechanisms of T helper cells by DNA
demethylation agent 5-Aza-2’-deoxycytidine in
experimental autoimmune encephalomyelitis
Advisor: Su-Fen Wu
Speaker: Chia-Bin Chang
Abstract：
Regulatory T (Treg) cells play an indispensable role in immune tolerance by
suppression of overt immune response after infection or autoimmune pathology.
Forkhead
box
P3 (Foxp3)
is
the major transcription factor for the
development and function of Treg cells and has been identified as a specific marker
for Treg cells. Defective Treg suppressive functions were observed in many
autoimmune diseases including multiple sclerosis. Previous studies have indicated
that epigenetic modifications are involved in the regulation of Foxp3 expression.
Treatment with low dose of 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-2’-deoxycytidine
(5-Aza) in experimental autoimmune encephalomyelitis (EAE), a widely used animal
model for human multiple sclerosis, to evaluate the demethylation effect in
autoimmune therapy. Previous study in our Lab had showed that 5-Aza treatment
increased the Foxp3 expression in CD4+CD25- T cells In vitro and in vivo. We found
that 5-Aza-pretreated mouse delayed the onset of EAE. Furthermore, we used luxol
fast blue staining to observe the demyelination in central nervous system (CNS) and
found that control mouse with sever demyelination but 5-Aza treated mouse without
demyelination. Next, we evaluated the inflammatory responses in CNS, there was no
inflammation in 5-Aza treated mice because of the low expression level of
inflammatory cytokines could be detected, and on the contrary, control EAE mouse
expressed very high level of IFN-γand IL-17. Moreover, pretreatment with 5-Aza in
vivo enhanced the Treg cell suppressive function. We also found that 5-Aza mice had
less activated effect T cells. Therefore, pretreated with 5-Aza enhanced the
Treg-mediated suppression and provided a protective effect against pathogenic
lymphocyte in CNS, and as a result, decreased the occurrence of experimental
allergic encephalomyelitis.
----------------------------------------------------------------------------The modulatory mechanisms of T helper cells by DNA
demethylation agent 5-Aza-2’-deoxycytidine in
experimental autoimmune encephalomyelitis
Speaker: Chia-Bin Chang
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