| Summary: | 博士 === 國防醫學院 === 生命科學研究所 === 93 === ABSTRACT
Decoy receptor 3 (DCR3) halts both Fas ligand- and LIGHT-induced cell deaths, which are required for pancreatic cell damage in autoimmune diabetes. In order to directly investigate the therapeutic potential of DCR3 in preventing this disease, we generated transgenic non-obese diabetic (NOD) mice, which overexpressed DCR3 in cells. Transgenic DCR3 protected mice from spontaneous and cyclophosphamide-induced autoimmune diabetes in a dose-dependent manner, and significantly reduced the severity of insulitis. Local expression of the transgene did not alter the diabetogenic properties of systemic lymphocytes or the development of T-helper 1 or T-regulatory cells. More importantly, the transgenic islets had a higher transplantation success rate and survived for longer than wild-type islets. We have demonstrated for the first time that the immune-evasion function of DCR3 inhibits autoimmunity, and that genetic manipulation of grafts may improve the success and survival of islet transplants.
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