Expression of interferon-stimulated genes in insulitic pancreatic islets of patients recently diagnosed with type 1 diabetes

M Lundberg, L Krogvold, E Kuric, K Dahl-Jørgensen… - Diabetes, 2016 - Am Diabetes Assoc
Diabetes, 2016Am Diabetes Assoc
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 …
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.
Am Diabetes Assoc