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

Quah, Hong Sheng, Miranda-Hernandez, Socorro, Khoo, Aimee, Harding, Ashley, Fynch, Stacey, Elkerbout, Lorraine, Brodnicki, Thomas C., Baxter, Alan G., Kay, Thomas W.H., Thomas, Helen E., and Graham, Kate L. (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). pp. 1032-1040.

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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.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 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 β-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.

Item ID: 31440
Item Type: Article (Refereed Research - C1)
ISSN: 1939-327X
Funders: National Health and Medical Research Council of Australia (NHMRC), Juvenile Diabetes Research Foundation, Victorian Government's Operational Infrastructure Support Program
Date Deposited: 19 Jun 2014 05:48
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110703 Autoimmunity @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920104 Diabetes @ 100%
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