Wen Li, Peng Jian, Li Zhenjun, Wong F Susan
Section of Endocrinology, Yale University School of Medicine, New Haven, CT 06520, USA.
J Immunol. 2004 Mar 1;172(5):3173-80. doi: 10.4049/jimmunol.172.5.3173.
Viral infections have previously been implicated as a trigger of autoimmune diabetes. In this study, we compared a viral mimic with other microbial components derived from bacteria in triggering diabetes development in C57BL/6-rat insulin promoter-B7.1 mice that do not normally develop diabetes. It is striking that only the viral mimic induced the development of diabetes in our model system. Further mechanistic studies suggest that diabetes is induced, in part, by the combination of direct recognition of this virus-like stimulus by pancreatic islets through the expression of the innate immune receptor, Toll-like receptor 3. In addition, the functions of APCs are up-regulated, and this could stimulate islet Ag-reactive T cells that will attack beta cells leading to autoimmune diabetes.
病毒感染此前一直被认为是自身免疫性糖尿病的触发因素。在本研究中，我们将一种病毒模拟物与源自细菌的其他微生物成分进行比较，以观察它们在通常不会发生糖尿病的C57BL/6-大鼠胰岛素启动子-B7.1小鼠中引发糖尿病发展的情况。令人惊讶的是，在我们的模型系统中，只有病毒模拟物诱导了糖尿病的发生。进一步的机制研究表明，糖尿病的诱导部分是由于胰岛通过天然免疫受体Toll样受体3的表达直接识别这种病毒样刺激物。此外，抗原呈递细胞（APC）的功能上调，这可能刺激胰岛抗原反应性T细胞，这些T细胞会攻击β细胞，导致自身免疫性糖尿病。
