RNase L contributes to experimentally induced type 1 diabetes onset in mice

Chun Zeng, Xin Yi, Danny Zipris, Hongli Liu, Lin Zhang, Qiaoyun Zheng, Krishnamurthy Malathi, Ge Jin, Aimin Zhou

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

The cause of type 1 diabetes continues to be a focus of investigation. Studies have revealed that interferon α (IFNα) in pancreatic islets after viral infection or treatment with double-stranded RNA(dsRNA), amimicof viral infection, is associatedwiththeonset of type1diabetes.However, how IFNα contributes to the onset of type 1 diabetes is obscure. In this study, we found that 2-5A-dependent RNase L (RNase L), an IFNα-inducible enzyme that functions in the antiviral and antiproliferative activities of IFN, played an important role in dsRNA-induced onset of type 1 diabetes. Using RNase L-deficient, rat insulin promoter-B7.1 transgenic mice, which are more vulnerable to harmful environmental factors such as viral infection, we demonstrated that deficiency of RNase L in mice resulted in a significant delay of diabetes onset induced by polyinosinic:polycytidylic acid (poly I:C), a type of synthetic dsRNA, and streptozotocin, a drug which can artificially induce type 1-like diabetes in experimental animals. Immunohistochemical staining results indicated that the population of infiltrated CD8+T cells was remarkably reduced in the islets of RNase L-deficient mice, indicating that RNase L may contribute to type 1 diabetesonset throughregulatingimmune responses. Furthermore, RNase L was responsible for the expression of certain proinflammatory genes in the pancreas under induced conditions. Our findings provide new insights into the molecular mechanism underlying β-cell destruction and may indicate novel therapeutic strategies for treatment and prevention of the disease based on the selective regulation and inhibition of RNase L.

Original languageEnglish (US)
Pages (from-to)277-287
Number of pages11
JournalJournal of Endocrinology
Volume223
Issue number3
DOIs
StatePublished - 2014

Keywords

  • Immune cells
  • Interferon
  • Poly I:C
  • RNase L
  • Type 1 diabetes

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Fingerprint Dive into the research topics of 'RNase L contributes to experimentally induced type 1 diabetes onset in mice'. Together they form a unique fingerprint.

Cite this