Islet expression of type I interferon response sensors is associated with immune infiltration and viral infection in type 1 diabetes.
Islet expression of type I interferon response sensors is associated with immune infiltration and viral infection in type 1 diabetes.
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1型糖尿病中I型干扰素应答传感器的胰岛表达与免疫浸润和病毒感染相关
DOI：
10.1126/sciadv.abd6527
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发表时间：
2021-03
期刊：
影响因子：
13.6
通讯作者：
nPOD-Virus Group
中科院分区：
文献类型：
--
作者：
Apaolaza PS;Balcacean D;Zapardiel-Gonzalo J;Nelson G;Lenchik N;Akhbari P;Gerling I;Richardson SJ;Rodriguez-Calvo T;nPOD-Virus Group
干扰素反应传感器在1型糖尿病过程中表达于朗格汉斯胰岛。先前的研究结果表明，在1型糖尿病（T1D）中存在干扰素（IFN）信号，能够诱导慢性炎症并损害b细胞功能。在这里，我们测定了自身抗体阳性和T1D供者胰岛中IFN反应标记物MxA、PKR和hla - 1的表达。我们发现这些标记可以在同一胰岛中共表达，在含胰岛素的胰岛中更丰富，在患有胰岛素的胰岛中高度表达，并且它们的表达水平与肠病毒蛋白VP1的存在相关。这些标志物的表达与胰岛素分泌通路中多个基因的下调有关。干扰素反应和微生物应激反应的共存很可能导致胰岛免疫破坏。该研究强调了旨在消除T1D患者潜在持续性感染和减少炎症的治疗干预的重要性。
Interferon response sensors are expressed in the islet of Langerhans during the course of type 1 diabetes. Previous results indicate the presence of an interferon (IFN) signature in type 1 diabetes (T1D), capable of inducing chronic inflammation and compromising b cell function. Here, we determined the expression of the IFN response markers MxA, PKR, and HLA-I in the islets of autoantibody-positive and T1D donors. We found that these markers can be coexpressed in the same islet, are more abundant in insulin-containing islets, are highly expressed in islets with insulitis, and their expression levels are correlated with the presence of the enteroviral protein VP1. The expression of these markers was associated with down-regulation of multiple genes in the insulin secretion pathway. The coexistence of an IFN response and a microbial stress response is likely to prime islets for immune destruction. This study highlights the importance of therapeutic interventions aimed at eliminating potentially persistent infections and diminishing inflammation in individuals with T1D.
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影响因子：
4.6
作者：
Bankhead P;Loughrey MB;Fernández JA;Dombrowski Y;McArt DG;Dunne PD;McQuaid S;Gray RT;Murray LJ;Coleman HG;James JA;Salto-Tellez M;Hamilton PW
通讯作者：
Hamilton PW
影响因子：
2.9
作者：
Philips, Tiffany;Kusmartseva, Irina;Kaddis, John S.
通讯作者：
Kaddis, John S.
影响因子：
7.7
作者：
Lundberg, Marcus;Krogvold, Lars;Skog, Oskar
通讯作者：
Skog, Oskar
影响因子：
8.2
作者：
Marroqui, Laura;Dos Santos, Reinaldo S.;Eizirik, Decio L.
通讯作者：
Eizirik, Decio L.
DOI：
10.1073/pnas.1700878114
发表时间：
2017-04-04
影响因子：
11.1
作者：
Marro, Brett S.;Ware, Brian C.;Oldstone, Michael B. A.
通讯作者：
Oldstone, Michael B. A.