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bioRxiv · 10.1101/258525

Type-I interferons inhibit interleukin-10 signaling and favor type 1 diabetes development in NOD mice

Iglesias, M.·Arun, A.·Chicco, M.·Lam, B.·Talbot, C.·Ivanova, V.·Lee, W. P. A.·Brandacher, G.·Raimondi, G.
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Abstract

Destruction of insulin-producing {beta}-cells by autoreactive T lymphocytes leads to the development of type 1 diabetes. Type I interferons (TI-IFN) and interleukin-10 (IL-10) have been connected with the pathophysiology of this disease; however, their interplay in the modulation of diabetogenic T cells remains unknown. We have discovered that TI-IFN cause a selective inhibition of IL-10 signaling in effector and regulatory T cells, altering their responses. This correlates with diabetes development in NOD mice, where the inhibition is also spatially localized to T cells of pancreatic and mesenteric lymph nodes. IL-10 signaling inhibition is reversible and can be restored via blockade of TI-IFN/IFN-R interaction, paralleling with the resulting delay in diabetes onset and reduced severity. Overall, we propose a novel molecular link between TI-IFN and IL-10 signaling that helps better understand the complex dynamics of autoimmune diabetes development and reveals new strategies of intervention.\n\nAbbreviations

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Iglesias, M., Arun, A., Chicco, M., Lam, B., Talbot, C., Ivanova, V., Lee, W. P. A., Brandacher, G., Raimondi, G.. 2018-02-01. Type-I interferons inhibit interleukin-10 signaling and favor type 1 diabetes development in NOD mice. https://doi.org/10.1101/258525

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