Poster Presentation The 13th International Congress of the Immunology of Diabetes Society 2013

IL-23 receptor signalling promotes pathogenic T cell responses and type 1 diabetes in NOD mice  (#188)

Andrew PR Sutherland 1 2 , Gerd Meyer zu Horste 2 , Nicole Joller 2 , Yasuhiro Kishi 2 , Vijay Kuchroo 2
  1. St Vincent's Institute, Fitzroy, VIC, Australia
  2. Center for Neurological Diseases, Brigham and Womens, Boston, Massachusetts, United States

Type 1 diabetes (T1D) is an autoimmune syndrome resulting in pancreatic β-cell destruction and the Non-Obese Diabetic (NOD) mouse model provides important mechanistic insights into human T1D. Effector and regulatory CD4+ T cells are critical regulators of T1D pathogenesis. Th17 cells promote tissue inflammation via the production of cytokines (eg IL-17A/F, IL-22, IL-21) and their function is fundamentally dependent upon IL-23R signalling in vivo. Th17 cells are implicated in the pathogenesis of T1D as the frequency of Th17 cells is increased in human T1D patients, however IL-17A deficient NOD mice are not protected from T1D and Th17 cells are associated with protection from T1D in NOD mice after bacterial colonisation. Thus our aim was to more fully elucidate the role of IL-23R and Th17 cells in T1D in NOD mice.

We demonstrate that Th17 cells promote T1D in NOD mice and that IL-23 potentiates their pathogenicity. IL-23R deficient NOD exhibit reduced incidence of T1D resulting from CD4+ T cell intrinsic defects. Protection from T1D in IL-23R deficient NOD mice is associated with reduced frequencies of Th17 cells, while Th1 cells and Tregs were unaffected. Finally transcript profiling revealed reduced expression of Th17 cell associated genes in pancreas infiltrating CD4+ T cells from IL-23R deficient NOD mice. These data indicate that IL-23 and Th17 cells promote T1D in NOD mice and that they may constitute novel therapeutic targets for the treatment of human T1D.