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

点击翻译按钮获取中文摘要

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.