Interleukin-27 Is Essential for Type 1 Diabetes Development and Sjögren Syndrome-like Inflammation

Publication date: 3 December 2019Source: Cell Reports, Volume 29, Issue 10Author(s): Ashley E. Ciecko, Bardees Foda, Jennifer Y. Barr, Sheela Ramanathan, Mark A. Atkinson, David V. Serreze, Aron M. Geurts, Scott M. Lieberman, Yi-Guang ChenSummaryHuman genetic studies implicate interleukin-27 (IL-27) in the pathogenesis of type 1 diabetes (T1D), but the underlying mechanisms remain largely unexplored. To further define the role of IL-27 in T1D, we generated non-obese diabetic (NOD) mice deficient in IL-27 or IL-27Rα. In contrast to wild-type NOD mice, both NOD.Il27−/− and NOD.Il27ra−/− strains are completely resistant to T1D. IL-27 from myeloid cells and IL-27 signaling in T cells are critical for T1D development. IL-27 directly alters the balance of regulatory T cells (Tregs) and T helper 1 (Th1) cells in pancreatic islets, which in turn modulates the diabetogenic activity of CD8 T cells. IL-27 also directly enhances the effector function of CD8 T cells within pancreatic islets. In addition to T1D, IL-27 signaling in T cells is also required for lacrimal and salivary gland inflammation in NOD mice. Our study reveals that IL-27 contributes to autoimmunity in NOD mice through multiple mechanisms and provides substantial evidence to support its pathogenic role in human T1D.Graphical Abstract
Source: Cell Reports - Category: Cytology Source Type: research