锌转运体 8 的基因沉默可减轻 T1D 中的炎症并保护胰腺组织损伤。
Gene silencing of ZnT8 attenuates inflammation and protects pancreatic tissue injury in T1D.
机构信息
Department of Outpatient, The Third People's Hospital of Linyi, Linyi, Shandong, 276023, China.
Department of Orthopedics, The Third People's Hospital of Linyi, Linyi, Shandong, 276023, China.
出版信息
Immunol Lett. 2018 Jun;198:1-6. doi: 10.1016/j.imlet.2018.03.013. Epub 2018 Mar 27.
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.
T 淋巴细胞介导的炎症反应导致了 1 型糖尿病的发生。近年来，锌转运体 8（ZnT8）已成为人类 1 型糖尿病自身反应性 T 细胞的靶标。然而，ZnT8 在 1 型糖尿病中的调节作用尚未确定。我们提出一个假设，即 ZnT8 水平的改变是否可以减轻 1 型糖尿病中的炎症反应并保护胰腺组织损伤。在这项研究中，我们利用 ZnT8 shRNA 抑制 ZnT8 的表达，并检测 NOD 小鼠的炎症、葡萄糖耐量和胰腺组织。我们发现 ZnT8 shRNA 可减轻特异性 CD8+T 细胞的激活和细胞毒性。此外，通过在 NOD 小鼠中下调 ZnT8，ZnT8 shRNA 可保护葡萄糖耐量和胰腺组织损伤。因此，这些结果表明，RNAi 代表了一种有前途的降低 ZnT8 介导的炎症反应的靶点，并为 1 型糖尿病提供了新的治疗线索。
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