Elevated expression of mitochondrial double-stranded RNAs in Sjögren’s syndrome contributes to PKR activation and Type I IFN activation

Abstract

Sjӧgren’s syndrome (SS) is a systemic autoimmune disease that attacks exocrine organs and leads to chronic inflammation and decreased tear and saliva production. The disease is particularly challenging to tackle because it lacks objective biomarker for earlier diagnosis of disease, and also there are no effective therapeutics to treat Sjӧgren’s syndrome. In order to establish a potential biomarker for the onset of Sjӧgren’s syndrome, the mechanisms involved in pathogenesis of SS were studied. Based on the previous findings that a dsRNA-binding protein PKR-dependent inflammatory signals are highly activated in Sjӧ gren’s syndrome (Kiripolsky, et al. 2018), endogenous double-stranded RNAs (dsRNAs) expression levels are measured in SS model. Among several candidates of endogenous double-stranded RNAs, mitochondrial dsRNAs could be a strong candidate to trigger aberrant activation of PKR in Sjӧgren’s syndrome patients. Kim et al. (2018) have demonstrated that mitochondrial RNAs, which exist as intermolecular dsRNAs, can regulate PKR phosphorylation and its downstream signaling, especially under stress. In 3D model, the level of disruption of tight junction structures, as well as water-channel protein distribution will be further investigated to uncover the accountability of mitochondrial dsRNAs in causing dysfunctional salivary glands among Sjӧgren’s syndrome patients.