title: Expression of Interferon-Stimulated Genes in Insulitic Pancreatic Islets of Patients Recently Diagnosed With Type 1 Diabetes.
abstract: 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.
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors.forename: Marcus
authors.initials: M
authors.lastname: Lundberg
authors.affiliation: Division of Paediatric and Adolescent Medicine, Oslo University Hospital, Oslo, Norway Faculty of Medicine, University of Oslo, Oslo, Norway.
authors.forename: Lars
authors.initials: L
authors.lastname: Krogvold
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors.forename: Enida
authors.initials: E
authors.lastname: Kuric
authors.affiliation: Division of Paediatric and Adolescent Medicine, Oslo University Hospital, Oslo, Norway Faculty of Medicine, University of Oslo, Oslo, Norway.
authors.forename: Knut
authors.initials: K
authors.lastname: Dahl-Jørgensen
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden oskar.skog@igp.uu.se.
authors.forename: Oskar
authors.identifier: 0000-0001-9713-722X
authors.initials: O
authors.lastname: Skog
mesh_terms: D015088:2',5'-Oligoadenylate Synthetase / Q000235:genetics; D000328:Adult; D054357:Chemokine CXCL10 / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics / Q000502:physiology; D007372:Interferons / Q000378:metabolism*; D007515:Islets of Langerhans / Q000276:immunology / Q000378:metabolism*; D061346:Laser Capture Microdissection; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D050794:STAT1 Transcription Factor / Q000235:genetics; D051196:Toll-Like Receptor 3 / Q000235:genetics; D055815:Young Adult
chemical_list: D054357:Chemokine CXCL10; C490287:GBP1 protein, human; C062341:HLA-F antigens; D015395:Histocompatibility Antigens Class I; C468762:IFI6 protein, human; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D050794:STAT1 Transcription Factor; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; D007372:Interferons; C475085:OAS1 protein, human; D015088:2',5'-Oligoadenylate Synthetase; D019204:GTP-Binding Proteins