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.
- Hong Sheng Quah1,2,
- Socorro Miranda-Hernandez3,
- Aimee Khoo1,2,
- Ashley Harding1,2,
- Stacey Fynch1,
- Lorraine Elkerbout1,
- Thomas C Brodnicki1,2,
- Alan G Baxter3,
- Thomas WH Kay1,2,
- Helen E Thomas1,2,4 and
- Kate L Graham1,2,4⇑
- 1St Vincent’s Institute, Fitzroy, Australia.
- 2The University of Melbourne Department of Medicine, St. Vincent’s Hospital, Fitzroy, Australia
- 3Comparative Genomics Centre, James Cook University, Townsville, Australia
- Corresponding author: Kate Graham Email:
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.
- © 2013 by the American Diabetes Association.
Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.