| Summary: | 碩士 === 國防醫學院 === 微生物及免疫學研究所 === 100 === Type 1 diabetes (T1D) is an autoimmune disease mainly caused by the Th1 cell-dependent destruction of pancreatic insulin-producing cells. NOD mouse, spontaneously developing autoimmune diabetes, is a well-established animal model for human T1D. Interleukin-21(IL-21) is secreted by T cells and has been reported to affect the functions of myeloid and lymphoid cells. Recently, published reports further reveal that IL-21 is highly increased in autoimmune diabetes, indicating a critical role of IL-21 in the pathogenesis of T1D. However, the mechanism underlying IL-21 modulation in diabetes disease remains unclear. B lymphocyte-induced maturation protein-1(Blimp-1) is a master suppressor in the terminal differentiation of T cell lineages. Our previous results indicate that serum level of IL-21 is significantly upregulated in Blimp-1 conditional knockout (CKO) NOD mice. In contrast, it is remarkably downregulated in Blimp1 transgenic (Tg) mice. Additionally, in an activated manner, Il21 expression is excessively increased in CKO CD4+ T cells, whereas it is markedly attenuated in Tg cells suggesting a suppressive effect of Blimp-1 on IL-21 expression of CD4+ T cell. To further understand the molecular mechanism by which Blimp-1 regulation Il21 expression, we used the luciferase reporter assay, electronic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) for further analysis. So far, in EL4 cells, Blimp-1 also impedes Il21 promoter activity in an activated manner and the result of luciferase reporter and ChIP indicate that Blimp-1 direct binding to the Il21 promoter then significantly decrease Il21 promoter activity. Finally, Blimp-1 should potentially impair IL-21 expression in T cells of autoimmune disease, thus it may highlights an insight into developing therapeutic strategies against autoimmune diseases.
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