Expression of Interferon-Stimulated Genes in Insulitic Pancreatic Islets of Patients Recently Diagnosed With Type 1 Diabetes
Expression of Interferon-Stimulated Genes in Insulitic Pancreatic Islets of Patients Recently Diagnosed With Type 1 Diabetes
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DOI：
10.2337/db16-0616
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发表时间：
2016-10-01
期刊：
影响因子：
7.7
通讯作者：
Skog, Oskar
中科院分区：
文献类型：
--
作者：
Lundberg, Marcus;Krogvold, Lars;Skog, Oskar
在1型糖尿病(T1D)的炎症过程中，对胰岛的原发损伤导致先天免疫的激活被认为是重要的一步。这项研究的目的是检查干扰素(干扰素)刺激基因(ISGs)在受胰岛素炎影响的人T1D胰岛中是否过度表达。通过激光捕获显微切割和定量PCR阵列，84个被检查的患者中有23个ISGs被发现在参与糖尿病病毒检测(DiViD)研究的新发T1D活体患者的胰岛中过度表达至少五倍，与来自非糖尿病器官捐赠者的胰岛相比。大多数高表达的ISGs，包括GBP1、TLR3、OAS1、EIF2AK2、HLA-E、IFI6和STAT1，在胰岛核心区域的表达高于含有周围免疫细胞的胰岛周围区域。相反，T细胞趋化因子CXCL10在胰岛周围区域的表达几乎是胰岛区域的10倍，这可能是T细胞主要定位于该区域的部分原因。总之，新近发病的T1D患者的胰岛表现出ISGs的过度表达，其表达模式类似于感染病毒或暴露于干扰素-γ/白介素1-β或干扰素-α的胰岛。
A primary insult to the pancreatic islets of Langerhans, leading to the activation of innate immunity, has been suggested as an important step in the inflammatory process in type 1 diabetes (T1D). The aim of this study was to examine whether interferon (IFN)-stimulated genes (ISGs) are overexpressed in human T1D islets affected with insulitis. By using laser capture microdissection and a quantitative PCR array, 23 of 84 examined ISGs were found to be overexpressed by at least fivefold in insulitic islets from living patients with recent-onset T1D, participating in the Diabetes Virus Detection (DiViD) study, compared with islets from organ donors without diabetes. Most of the overexpressed ISGs, including GBP1, TLR3, OAS1, EIF2AK2, HLA-E, IFI6, and STAT1, showed higher expression in the islet core compared with the peri-islet area containing the surrounding immune cells. In contrast, the T-cell attractant chemokine CXCL10 showed an almost 10-fold higher expression in the peri-islet area than in the islet, possibly partly explaining the localization of T cells mainly to this region. In conclusion, insulitic islets from recent-onset T1D subjects show overexpression of ISGs, with an expression pattern similar to that seen in islets infected with virus or exposed to IFN-gamma/interleukin-1 beta or IFN-alpha.