Faculty Collaboration Database

Interleukin-27 Is Essential for Type 1 Diabetes Development and Sjögren Syndrome-like Inflammation. Cell Rep 2019 Dec 03;29(10):3073-3086.e5

Date

12/05/2019

Pubmed ID

31801074

Pubmed Central ID

PMC6914223

DOI

10.1016/j.celrep.2019.11.010

Scopus ID

2-s2.0-85075892781 (requires institutional sign-in at Scopus site)   31 Citations

Abstract

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.

Author List

Ciecko AE, Foda B, Barr JY, Ramanathan S, Atkinson MA, Serreze DV, Geurts AM, Lieberman SM, Chen YG

Authors

Yi-Guang Chen PhD Professor in the Pediatrics department at Medical College of Wisconsin
Aron Geurts PhD Professor in the Physiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

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