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

Cell Rep. 2019 Dec 3;29(10):3073-3086.e5. doi: 10.1016/j.celrep.2019.11.010.


Human 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.

Keywords: IL-27; IL-27Ra; NOD mouse; Sjögren syndrome; T cells; T-bet; autoimmunity; insulitis; type 1 diabetes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoimmunity / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Diabetes Mellitus, Type 1 / immunology*
  • Female
  • Inflammation / immunology*
  • Interleukins / immunology*
  • Islets of Langerhans / immunology
  • Male
  • Mice
  • Mice, Inbred NOD
  • Sjogren's Syndrome / immunology*
  • T-Lymphocytes, Regulatory / immunology
  • Th1 Cells / immunology


  • Il27 protein, mouse
  • Interleukins