Expression of Interferon-Stimulated Genes in Insulitic Pancreatic Islets of Patients Recently Diagnosed With Type 1 Diabetes

• Published in: Diabetes (New York, N.Y.) Vol. 65; no. 10; pp. 3104 - 3110
• Main Authors: Lundberg, Marcus, Krogvold, Lars, Kuric, Enida, Dahl-Jørgensen, Knut, Skog, Oskar
• Format: Journal Article
• Language: English
• Published: United States American Diabetes Association 01.10.2016
• Subjects: 2',5'-Oligoadenylate Synthetase - genetics; Adult; Chemokine CXCL10 - genetics; Cytokines; Diabetes; Diabetes Mellitus, Type 1 - genetics; Female; Gene expression; GTP-Binding Proteins - genetics; Histocompatibility Antigens Class I - genetics; Humans; Immunity (Disease); Immunity, Innate - genetics; Immunity, Innate - physiology; Interferons - metabolism; Islets of Langerhans - immunology; Islets of Langerhans - metabolism; Laser Capture Microdissection; Lymphocytes; Male; Middle Aged; Mitochondrial Proteins - genetics; RNA, Messenger - genetics; STAT1 Transcription Factor - genetics; Toll-Like Receptor 3 - genetics; Viruses; Young Adult
• DOI: 10.2337/db16-0616
• ISSN: 0012-1797; 1939-327X

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.