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

  1. Kate L Graham1,2,4
  1. 1St Vincent’s Institute, Fitzroy, Australia.
  2. 2The University of Melbourne Department of Medicine, St. Vincent’s Hospital, Fitzroy, Australia
  3. 3Comparative Genomics Centre, James Cook University, Townsville, Australia
  1. Corresponding author: Kate Graham Email: kgraham{at}


Type I interferons (IFN) have been implicated in initiation of islet autoimmunity and development of type 1 diabetes (T1D). To directly test their involvement, we generated NOD mice deficient in type I IFN receptors (NOD.IFNAR1-/-). 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 Ifnα 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.IFNAR1-/- islets. Loss of TLR2 resulted in reduced islet expression of Mx1 at 2 weeks of age, but TLR2 or TLR9-deficiency did not change expression of other IFN-induced genes in islets compared with wild-type NOD islets. We observed increased β cell MHC class I expression with age in both NOD and NOD.IFNAR1-/- mice. NOD.IFNAR1-/- mice developed insulitis and diabetes at a similar rate to NOD controls. These results indicate type I IFN is produced within islets in young mice, but is not essential for the initiation and progression of diabetes in NOD mice.


  • 4These authors contributed equally

  • Received August 7, 2013.
  • Accepted November 3, 2013.

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