Interferons are key cytokines acting on pancreatic islets in type 1 diabetes

• DOI: 10.1007/s00125-024-06106-7
• Publication Date: 2024-02-26T20:02:01Z
• Authors: Alexandra Coomans...; Maria Ines Alvelos; Florian Szymczak; Priscila L. Zimath; Angela Castela; Bianca Marmontel ...; Arturo Roca Rivada; Sandra Marín-Cañas; Xiaoyan Yi; Anne Op de Beeck; Noel G. Morgan; Sebastian Sonntag; Sayro Jawurek; Alexandra C. Title; Burcak Yesildag; François Pattou; Julie Kerr-Conte; Eduard Montanya; Montserrat Nacher; Lorella Marselli; Piero Marchetti; Sarah J. Richardson; Decio L. Eizirik
• Keywords: Pancreatic Islets; Human physiology

AbstractThe pro-inflammatory cytokines IFNα, IFNγ, IL-1β and TNFα may contribute to innate and adaptive immune responses during islet inflammation (insulitis) in type 1 diabetes (T1D). We used deep RNA-sequencing analysis to characterize the response of human pancreatic beta cells to each cytokine individually and compared the signatures obtained with those present in islets of individuals affected by T1D. IFNα and IFNγ had a much greater impact on the beta cell transcriptome when compared to IL-1β and TNFα. The IFN-induced gene signatures have a strong correlation with those observed in beta cells from T1D patients, and the level of expression of specific IFN-stimulated genes is positively correlated with proteins present in islets of these individuals, regulating beta cell responses to “danger signals” such as viral infections. These data suggest that IFNα and IFNγ are the central cytokines at the islet level in T1D, contributing to the triggering and amplification of autoimmunity.