Details

Autor(en) / Beteiligte

• Ciecko, Ashley E.
• Foda, Bardees
• Barr, Jennifer Y.
• Ramanathan, Sheela
• Atkinson, Mark A.
• Serreze, David V.
• Geurts, Aron M.
• Lieberman, Scott M.
• Chen, Yi-Guang

Titel

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

Ist Teil von

• Cell reports (Cambridge), 2019-12, Vol.29 (10), p.3073-3086.e5

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2019

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. [Display omitted] •NOD mice deficient in IL-27 or IL-27Rα are completely resistant to type 1 diabetes•T cell-intrinsic IL-27 signaling is essential for type 1 diabetes development•IL-27 directly alters the balance of Treg and effector T cells to favor the latter•T cells require IL-27 signaling for Sjögren syndrome-like inflammation in NOD mice Human genetic studies implicate IL-27 in the pathogenesis of type 1 diabetes (T1D). Ciecko et al. demonstrate that IL-27 signaling in T cells changes the balance of regulatory and effector subsets and is critical for T1D development as well as lacrimal and salivary gland inflammation in NOD mice.