Gene silencing of ZnT8 attenuates inflammation and protects pancreatic tissue injury in T1D.

T lymphocyte mediated inflammation contributes to the development of T1D. Zinc Transporter 8 (ZnT8) has emerged as a target of autoreactive T cells in human T1D in recent years. However, the regulating of ZnT8 in T1D has not been identified. We make a hypothesis that whether alternation of ZnT8 level could attenuate inflammation and protect pancreatic tissue injury in T1D. In this study, we utilized ZnT8 shRNA to inhibit ZnT8 expression, and detected inflammation, glucose tolerance and pancreatic tissue of NOD mice. We found that ZnT8 shRNA attenuated specific CD8+ T cell activation and cytotoxicity. In addition, ZnT8 shRNA protected glucose tolerance and pancreatic tissue injury via down-regulation of ZnT8 in NOD mice. Therefore, the results suggest that RNAi represents a promising target reducing ZnT8 mediated inflammation, and provides a novel therapeutical clue in T1D.