IFNβ accelerates autoimmune type 1 diabetes in nonobese diabetic mice and breaks the tolerance to β cells in nondiabetes-prone mice

Aurora Alba, M. Carmen Puertas, Jorge Carrillo, Raquel Planas, Rosa Ampudia, Xavier Pastor, Fatima Bosch, Ricardo Pujol-Borrell, Joan Verdaguer, Marta Vives-Pi

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44 Citations (Scopus)

Abstract

Genetic and environmental factors are decisive in the etiology of type 1 diabetes. Viruses have been proposed as a triggering environmental event and some evidences have been reported: type I IFNs exist in the pancreata of diabetic patients and transgenic mice expressing these cytokines in β cells develop diabetes. To determine the role of IFNβ in diabetes, we studied transgenic mice expressing human IFNβ in the β cells. Autoimmune features were found: MHC class I islet hyperexpression, T and B cells infiltrating the islets and transfer of the disease by lymphocytes. Moreover, the expression of β2-microglobulin, preproinsulin, and glucagon in the thymus was not altered by IFNβ, thus suggesting that the disease is caused by a local effect of IFNβ, strong enough to break the peripheral tolerance to β cells. This is the first report of the generation of NOD (a model of spontaneous autoimmune diabetes) and nonobese-resistant (its homologous resistant) transgenic mice expressing a type I IFN in the islets: transgenic NOD and nonobese-resistant mice developed accelerated autoimmune diabetes with a high incidence of the disease. These results indicate that the antiviral cytokine IFNβ breaks peripheral tolerance to β cells, influences the insulitis progression and contributes to autoimmunity in diabetes and nondiabetes- prone mice.
Original languageEnglish
Pages (from-to)6667-6675
JournalJournal of Immunology
Volume173
Issue number11
Publication statusPublished - 1 Dec 2004

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