Deficiency in type I interferon signalling prevents the early interferon-gene signature in pancreatic islets but not type 1 diabetes in non-obese diabetic mice. — ASN Events

Deficiency in type I interferon signalling prevents the early interferon-gene signature in pancreatic islets but not type 1 diabetes in non-obese diabetic mice. (#278)

Hong Sheng Quah 1 , Stacey Fynch 1 , Lorraine Elkerbout 1 , Thomas C Brodnicki 1 , Thomas W Kay 1 , Helen E Thomas 1 , Kate L Graham 1
  1. St Vincent's Institute of Medical Research, Fitzroy, VIC, Australia
Type 1 diabetes (T1D) is caused by the autoimmune destruction of insulin-producing beta cells by immune cells that infiltrate into the pancreatic islets. During islet infiltration, immune cells and beta cells can produce proinflammatory cytokines. Type I interferons (IFN) have been implicated in initiation of islet autoimmunity and development of T1D. To directly test its involvement, we generated NOD mice deficient in type I IFN receptors (NOD.IFNAR1). We studied expression of type I IFN-induced genes in islets isolated from 2 to 6 week-old NOD and B6 mice. Expression of Mx1, Isg15, Ifit1 and Oas1a was detectable in islets as early as 2 weeks of age, peaked at 3-4 weeks of age and declined at 5-6 weeks of age. The gene expression was significantly reduced in NOD.IFNAR1 islets. However, this gene signature was also observed in islets from B6 and B6.IFNAR1 mice, which are not prone to autoimmunity, indicating the contribution of type I IFN signalling within islets from young mice is not autoimmune-regulated. Type I IFNs may contribute to upregulation of MHC class I on beta cells to increase their recognition by CD8+ T cells. MHC class I expression increased with age in both NOD and NOD.IFNAR1 mice aged, indicating type I IFNs are not required for its upregulation. NOD.IFNAR1 mice developed T1D and islet infiltration at a similar rate to NOD controls. These results indicate the IFN gene signature observed in islets from young mice may be developmentally regulated, and type I IFN is not the main driver of islet autoimmunity in NOD mice.
@ADSADEA