TypeⅠinterferons in the pathogenesis of pediatric autoimmune diseases : Insights from Mendelian interferonopathies.

Abstract

Type I interferonopathy is a group of Mendelian inflammatory disorders where chronic and autonomous enhancement of type I interferon （IFN） production is central to the pathogenesis. In these disorders, upregulation of type I IFN signaling can occur due to abnormal accumulation of endogenous nucleic acids, inappropriate stimulation or defective negative regulation of type I IFN signaling pathway, and defective proteasome activities. Upregulated type I IFN signaling has also been identified in autoimmune diseases including SLE and dermatomyositis, suggesting strong association between IFN and development of these diseases. Conversely, some type I interferonopathies develop similar symptoms as SLE and other autoimmune diseases, suggesting these non-genetic diseases have the same or similar underlying mechanism of enhanced type I IFN signaling. In this review, we focus on molecular mechanisms leading to activation of type I IFN signaling in the pathogenesis of interferonopathies and autoimmune diseases.