Expression of Toll-like Receptors in the Pancreas of Recent-onset Fulminant Type 1 Diabetes
Expression of Toll-like Receptors in the Pancreas of Recent-onset Fulminant Type 1 Diabetes
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DOI：
10.1507/endocrj.k09e-291
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发表时间：
2010-03-20
影响因子：
2
通讯作者：
Hanafusa, Toshiaki
中科院分区：
文献类型：
--
作者：
Shibasaki, Saeko;Imagawa, Akihisa;Hanafusa, Toshiaki
暴发性1型糖尿病，建立于2000年，被定义为糖尿病的一种新亚型，其由疾病发作时胰腺β细胞的显著急性和几乎完全破坏引起。在这项研究中，我们的目的是澄清暴发性1型糖尿病的发病机制，特别是胰岛炎和病毒感染。我们检查了胰腺尸检样本，从三个病人谁已经死亡后不久，疾病的发病和分析这些免疫组织化学和原位杂交。结果是，与正常对照组相比，β和α细胞面积均显著减少。发病后即刻患者β细胞平均面积仅为0.00256%，而正常对照组为1.745%。巨噬细胞和T细胞，但没有自然杀伤细胞浸润胰岛和外分泌胰腺。虽然他们都有大量的浸润，巨噬细胞占主导地位的胰岛浸润，并在92.6%的患者的胰岛中检测到。Toll样受体（TLR）3是一种病毒成分的传感器，在所有3例患者中，在84.7+/-7.0%的巨噬细胞和62.7+/-32.3%的T细胞中检测到（平均值+/-SD）。TLR 7和TLR 9也在所有三名患者的胰腺中检测到。通过原位杂交，在3例患者中的1例患者的β细胞阳性胰岛中检测到肠道病毒RNA。总之，我们的研究结果表明，巨噬细胞为主的胰岛炎，而不是T细胞自身免疫有助于β细胞破坏暴发型1型糖尿病。
Fulminant type 1 diabetes, established in 2000, is defined as a novel subtype of diabetes mellitus that results from remarkably acute and almost complete destruction of pancreatic beta cells at the disease onset. In this study, we aimed to clarify the pathogenesis of fulminant type 1 diabetes with special reference to insulitis and viral infection. We examined pancreatic autopsy samples from three patients who had died soon after the onset of disease and analyzed these by immunohistochemistry and in situ hybridization. The results were that both beta and alpha cell areas were significantly decreased in comparison with those of normal controls. Mean beta cell area of the patients just after the onset was only 0.00256% while that of normal control was 1.745%. Macrophages and T cells-but no natural killer cells had infiltrated the islets and the exocrine pancreas. Although both of them had massively infiltrated, macrophages dominated islet infiltration and were detected in 92.6% of the patients' islets. Toll-like receptor (TLR) 3, a sensor of viral components, was detected in 84.7+/-7.0% of macrophages and 62.7+/-32.3% of T cells (mean+/-SD) in all three patients. TLR7 and TLR9 were also detected in the pancreas of all three patients. Enterovirus RNA was detected in beta-cell positive islets in one of the three patients by in situ hybridization. In conclusion, our results suggest that macrophage-dominated insulitis rather than T cell autoimmunity contributes to beta cell destruction in fulminant type 1 diabetes.