| First Author | Quah HS | Year | 2014 |
| Journal | Diabetes | Volume | 63 |
| Issue | 3 | Pages | 1032-40 |
| PubMed ID | 24353186 | Mgi Jnum | J:209067 |
| Mgi Id | MGI:5565629 | Doi | 10.2337/db13-1210 |
| Citation | Quah HS, et al. (2014) Deficiency in type I interferon signaling prevents the early interferon-induced gene signature in pancreatic islets but not type 1 diabetes in NOD mice. Diabetes 63(3):1032-40 |
| abstractText | 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.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 Ifnalpha 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 Toll-like receptor 2 (TLR2) resulted in reduced islet expression of Mx1 at 2 weeks of age, but TLR2 or TLR9 deficiency did not change the expression of other IFN-induced genes in islets compared with wild-type NOD islets. We observed increased beta-cell major histocompatibility complex class I expression with age in 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. |
