ePoster Presentation 49th Annual Scientific Meeting of the Australian and New Zealand Society for Immunology 2021

Identifying the functional roles of IL-17RA in type 1 diabetes (#232)

Sangjong Yu 1 2 , Andrew PR Sutherland 1 2
  1. University of Mebourne, Melbourne, VIC, Australia
  2. St Vincent’s Institute of Medical Research, FItzroy, VIC, Australia

Type 1 diabetes (T1D) is an organ-specific autoimmune disease in which insulin-producing pancreatic b-cells are the target of a destructive autoimmune response. Cytokines and cytokine receptors play critical roles in the activation and differentiation of autoreactive T and B cells, which are central to the pathogenesis of T1D. Previous studies have identified roles for the cytokine IL-17A in Non-Obese Diabetic (NOD) mice however the functions of IL-17 receptors in the context of T1D have not been studied to date. Here we show that IL-17 receptor A (IL-17RA), a receptor for IL-17A, is expressed on multiple lymphocyte lineages that regulate the development of T1D in Non-Obese Diabetic (NOD) mice, including CD4+ and CD8+ T cells, B cells and innate immune cells. Phenotypic profiling of IL-17RA expressing T cells revealed that IL-17RA was predominantly expressed by antigen-experienced T cells. IL-17RA is upregulated on T and B cells in vitro in response to antigen receptor activation or stimulation with IL-21, a cytokine that regulates lymphocyte effector differentiation in T1D. Consistent with these findings, islet autoantigen specific CD4+ and CD8+ T cells in pancreatic islets of NOD mice exhibit increased expression of IL-17RA. Together, these observations suggest that IL-17RA may regulate the function of islet antigen reactive T cells and B cells. To determine how IL-17RA contributes to the development of T1D we generated IL-17RA deficient NOD mice. These mice exhibited a significant reduction in insulin autoantibody levels and are strongly protected from the development of T1D. These data indicate that IL-17RA has important roles in T1D development in NOD mice, potentially via functional impairment of autoreactive T and B cells.