@article{7fc38fa1a9f64fd780c64dde9ca48956,
title = "Type-I interferons inhibit interleukin-10 signaling and favor Type 1 diabetes development in nonobese diabetic mice",
abstract = "Destruction of insulin-producing β-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 nonobese diabetic 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.",
keywords = "Interleukin-10 signaling, Nonobese diabetic mice, T lymphocytes, Type 1 diabetes, Type-I interferons",
author = "Marcos Iglesias and Anirudh Arun and Maria Chicco and Brandon Lam and Talbot, {C. Conover} and Vera Ivanova and Lee, {W. P.A.} and Gerald Brandacher and Giorgio Raimondi",
note = "Funding Information: The authors thank Sonia Santiago (laboratory manager), and Xiaoling Zhang (flow cytometry specialist), both at Johns Hopkins University, for excellent technical assistance; Dawn Hull and Kamal Abdi (animal facility supervisors; Johns Hopkins University) for animal husbandry and care; and Dr. Mark Donowitz (for granting access to his Odyssey CLx LI-COR). We would also like to thank Dr. Ranjeny Thomas (University of Queensland, Australia), Dr. John Alcorn (University of Pittsburgh), Drs. Alan Scott, Thomas Donner, Edward Harhaj, Erika Darrah, Tory Johnson (Johns Hopkins University), Dr. Francesca Granucci (University of Milano-Bicocca, Italy), and Dr. Ivan Zanoni (Harvard University) for invaluable feedback on experimental design, troubleshooting, and manuscript preparation This work was supported by American Diabetes Association Junior Faculty Award 1-10-JF-43, a Starzl Transplantation Institute Joseph Patrick Fellowship, a Pilot and Feasibility Grant from the Baltimore Diabetes Research Center, an American Association of Immunologists 2016-2017 Careers in Immunology Fellowship, and JDRF strategic research agreement 2-SRA-2016-304-S-B (all to GR). Publisher Copyright: {\textcopyright} 2018 Iglesias, Arun, Chicco, Lam, Talbot, Ivanova, Lee, Brandacher and Raimondi.",
year = "2018",
month = jul,
day = "16",
doi = "10.3389/fimmu.2018.01565",
language = "English (US)",
volume = "9",
journal = "Frontiers in immunology",
issn = "1664-3224",
publisher = "Frontiers Media S. A.",
number = "JUL",
}