Expression of Interferon-Stimulated Genes in Insulitic Pancreatic Islets of Patients Recently Diagnosed With Type 1 Diabetes
| Autor: | Knut Dahl-Jørgensen, Oskar Skog, Lars Krogvold, Enida Kuric, Marcus Lundberg |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Adult Male endocrine system Chemokine endocrine system diseases Endocrinology Diabetes and Metabolism 030209 endocrinology & metabolism Laser Capture Microdissection Mitochondrial Proteins 03 medical and health sciences Islets of Langerhans Young Adult 0302 clinical medicine Immune system Interferon GTP-Binding Proteins Internal Medicine medicine 2' 5'-Oligoadenylate Synthetase CXCL10 Humans RNA Messenger Laser capture microdissection geography geography.geographical_feature_category biology Pancreatic islets Histocompatibility Antigens Class I Middle Aged medicine.disease Islet Immunity Innate Toll-Like Receptor 3 Chemokine CXCL10 030104 developmental biology medicine.anatomical_structure Diabetes Mellitus Type 1 STAT1 Transcription Factor Immunology biology.protein Female Interferons Insulitis medicine.drug |
| Zdroj: | Diabetes. 65(10) |
| ISSN: | 1939-327X |
| Popis: | 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-γ/interleukin-1β or IFN-α. |
| Databáze: | OpenAIRE |
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