CMCB Life Sciences Seminar: Dr. Yuval Dor, The Hebrew University of Jerusalem, Faculty of Medicine, Israel

Hosts: Karsten Kretschmer & Nikolay Ninov (CRTD)

Title: “Impaired RNA editing as a path to islet inflammation and diabetes”

Abstract: A major hypothesis for the etiology of type 1 diabetes (T1D) postulates initiation by viral infection, leading to double-stranded RNA (dsRNA)-mediated interferon response and inflammation; however, a causal virus has not been identified. We have used a mouse model, corroborated with human islet data, to demonstrate that endogenous dsRNA in beta cells can lead to a diabetogenic immune response, thus identifying a virus-independent mechanism for T1D initiation. We found that disruption of the RNA editing enzyme ADAR in beta cells triggers a massive interferon response, islet inflammation and beta cell failure and destruction, with features bearing striking similarity to early-stage human T1D. Glycolysis via calcium enhances the interferon response, suggesting an actionable vicious cycle of inflammation and increased beta cell workload. Thus, defects in RNA editing in beta cell may lead to the accumulation of endogenous dsRNA and to islet inflammation and diabetes. I will present published and unpublished data supporting the hypothesis that defects in RNA editing may contribute to early stages of T1D, and shed light on unexplained T1D phenomena.