Author:
Coomans de Brachène Alexandra,Alvelos Maria Ines,Szymczak Florian,Zimath Priscila Laiz,Castela Angela,Marmontel de Souza Bianca,Roca Rivada Arturo,Marín-Cañas Sandra,Yi Xiaoyan,Op de Beeck Anne,Morgan Noel G.,Sonntag Sebastian,Jawurek Sayro,Title Alexandra C.,Yesildag Burcak,Pattou François,Kerr-Conte Julie,Montanya Eduard,Nacher Montserrat,Marselli Lorella,Marchetti Piero,Richardson Sarah J.,Eizirik Decio L.
Abstract
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.
Publisher
Cold Spring Harbor Laboratory