Transgenic expression of decoy receptor 3 protects islets from spontaneous and chemical-induced autoimmune destruction in non-obese diabetic mice

• Main Authors: Hsiang-Hsuan Sung, 宋向軒
• Other Authors: Huey-Kang Sytwu, M.D., Ph. D.
• Format: Others
• Language: zh-TW
• Published: 2005
• Online Access: http://ndltd.ncl.edu.tw/handle/77350581527916851707

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.