Potential role of type I interferon in the pathogenic process leading to type 1 diabetes.

Abstract

Understanding the relationship between viral infections and the development of type 1 diabetes (T1D) is essential for T1D prevention. Virus-induced innate immune responses, specifically type I interferon (IFN-I) and the IFN gene signature, orchestrate early events of β-cell dysfunction preceding islet autoimmunity. We summarize recent advances in how IFN-I and the IFN gene signature can drive T1D development. IFN-I, particularly IFN-α, and the IFN gene signature have been detected in islets and peripheral blood of T1D patients. T1D risk genes in the IFN-I signaling pathway regulate antiviral responses in β cells driven by IFN-I and proinflammatory cytokines. Polymorphisms in these genes may cause chronic dysregulated IFN signaling in islets, characterized by hyperexpression of IFN-I, the IFN gene signature, and major histocompatibility complex class I during viral infection. Islet-cell inflammation mediated by aberrant IFN signaling drives β-cell apoptosis by initiating autoreactivity against β-cell antigens. The profound elevation in IFN-I and the IFN gene signature observed in some forms of T1D are also seen in a novel group of human autoimmune and autoinflammatory diseases called interferonopathies. Despite significant advances, further studies are required to functionally dissect the mechanisms by which excessive IFN-I contributes to the evolution of autoimmunity that destroys β cells.