The type 1 diabetes-associated lncRNA ARGI participates in virus-induced pancreatic β cell inflammation.

We performed the functional characterization of a virus-induced T1D-associated lncRNA named ARGI (Antiviral Response Gene Regulator). ARGI overexpression in pancreatic beta cells leads to the transcriptional activation of several antiviral genes, including genes of the T1D-associated IRF7-driven inflammatory gene network (IDIN). Upon a viral insult, ARGI is upregulated in the nuclei of pancreatic beta cells and binds to the transcription factor CTCF to interact with the regulatory regions of IFN and interferon-stimulated genes (ISGs), promoting their transcriptional activation in an allele-specific manner. The presence of the T1D risk allele in ARGI induces a hyperactivation of the antiviral and type I IFN response genes in beta cells, an expression signature that is typically overserved in the pancreas of T1D patients. Comparative gene expression profiling analysis of RNA-seq data for EndoC-βH1 human pancreatic beta cell line, between control condition and ARGI overexpression