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

Coomans de Brachene, A.; Alvelos, M. I.; Szymczak, F.; Zimath, P. L.; Castela, A.; Marmontel de Souza, B.; Roca Rivada, A.; Marin-Canas, S.; Yi, X.; Op de Beeck, A.; Morgan, N. G.; Sonntag, S.; Jawurek, S.; Title, A. C.; Yesildag, B.; Pattou, F.; Kerr-Conte, J.; Montanya, E.; Nacher, M.; Marselli, L.; Marchetti, P.; Richardson, S. J.; Eizirik, D. L.

doi:10.1101/2023.06.29.547000

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bioRxiv · 10.1101/2023.06.29.547000

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

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Abstract

The pro-inflammatory cytokines IFN, IFN{gamma}, IL-1{beta} and TNF 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. IFN and IFN{gamma} had a much greater impact on the beta cell transcriptome when compared to IL-1{beta} and TNF. 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 IFN and IFN{gamma} are the central cytokines at the islet level in T1D, contributing to the triggering and amplification of autoimmunity.

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Coomans de Brachene, A., Alvelos, M. I., Szymczak, F., Zimath, P. L., Castela, A., Marmontel de Souza, B., Roca Rivada, A., Marin-Canas, S., Yi, X., Op de Beeck, A., Morgan, N. G., Sonntag, S., Jawurek, S., Title, A. C., Yesildag, B., Pattou, F., Kerr-Conte, J., Montanya, E., Nacher, M., Marselli, L., Marchetti, P., Richardson, S. J., Eizirik, D. L.. 2023-07-01. Interferons are the key cytokines acting on pancreatic islets in type 1 diabetes. https://doi.org/10.1101/2023.06.29.547000

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