Deficiency in type i interferon signaling prevents the early interferon-induced gene signature in pancreatic islets but not type 1 diabetes in NOD mice

Abstract

Type I interferons (IFNs) have been implicated in the initiation of islet autoimmunity and development of type 1 diabetes. To directly test their involvement, we generated NOD mice deficient in type I IFN receptors (NOD.IFNAR12/2). Expression of the type I IFN-induced genes Mx1, Isg15, Ifit1, Oas1a, and Cxcr4 was detectable in NOD islets as early as 1 week of age. Of these five genes, expression of Isg15, Ifit1, Oas1a, and Mx1 peaked at 3-4 weeks of age, corresponding with an increase in Ifna mRNA, declined at 5-6 weeks of age, and increased again at 10-14 weeks of age. Increased IFN-induced gene expression was ablated in NOD.IFNAR12/2 islets. Loss of Toll-like receptor 2 (TLR2) resulted in ..