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.