Expression of Interferon-Stimulated Genes in Insulitic Pancreatic Islets of Patients Recently Diagnosed with Type 1 Diabetes
A primary insult to the pancreatic islets of Langerhans, leading to 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-stimulated genes (ISGs) are overexpressed in human T1D islets affected with insulitis. By employing laser capture microdissection and qPCR array, 23 out of 84 examined ISGs were found to be overexpressed at least 5-fold in insulitic islets from living patients with recent onset T1D, participating in the Diabetes Virus Detection (DiViD) study, compared to in islets from non-diabetic organ donors. Most of the overexpressed ISGs, including GBP1, TLR3, OAS1, EIF2AK2, HLA-E, IFI6 and STAT1, showed higher expression in the islet core compared to in 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 explaining partly 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 IFNγ/IL1β or IFNα.
§ KDJ is the principal investigator of the DiViD study.
- Received May 13, 2016.
- Accepted July 7, 2016.
- © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.