The role of dsRNA sensor in dendritic cells in a tolerized model of Type 1 diabetes

我们发现，作为1型糖尿病小鼠模型，给予抗Fas抗体完全抑制了NOD小鼠的糖尿病发病。此外，注射来自Fas缺陷的NOD-LPR小鼠的骨髓来源的树突状细胞也完全保护了NOD小鼠的糖尿病发病。为了评价TLR3作为树突状细胞dsRNA传感器的作用，首先在NOD小鼠体内注射Poly(I：C)作为TLR3激动剂。低剂量的聚(I：C)抑制NOD小鼠的糖尿病发病，而高剂量的聚(I：C)加速NOD小鼠的糖尿病发病。接下来，为了评估TLR3在耐受的1型糖尿病小鼠模型中的作用，在耐受的小鼠中进行了大剂量聚(I：C)的给药。令人惊讶的是，我们发现高剂量的Poly(I：C)诱导了糖尿病，并打破了经抗Fas抗体治疗的耐受性NOD小鼠的耐受性。我们证明了dsRNA传感器在1型糖尿病发生发展中的重要性。

We found that administration of anti-Fas Ab completely suppressed diabetic onset in NOD mice as a type 1 diabetic mouse model. In addition, administration of bone marrow derived dendritic cells from Fas-deficient NOD-lpr mice which is diabetes-free also comletely protected from diabetes onset in NOD mice. To evaluate the role of TLR3 as dsRNA sensor of dendritic cells, administration n of poly (I:C) as TLR3 agonist in NOD mice was performed firstly. Low dose of poly(I:C) suppressed diabetes onset in NOD mice, whereas high dose of poly(I:C) accelerated diabetes onset in NOD mice. Next, to evaluate the role of TLR3 in a tolerized mouse model of type 1 diabetes, administartion of high dose of poly(I:C) was performed in tolerized mice. Surprisingly, we found that high dose of poly(I:C) induced diabetes and broke tolerance in tolerized NOD mice treated with anti-Fas Ab. We demonstrated the importance of dsRNA sensor in the development of type 1 diabetes.