Although the pancreas expresses high levels of IL-22 receptor (IL-22Rα2), the role of IL-22 in the pancreas remains elusive. We found elevated levels of IL-22-producing Th17 cells infiltrating the islets in diabetic NOD mice. We used an adoptive transfer system to explore the role of these cells in pancreas. Naive T cells from BDC2.5 transgenic mice were differentiated into effector Th17 (Teff17) cells by IL-23 plus IL-6 in vitro. These polarized cells produced large amounts of IL-22 and upon adoptive transfer into wild type NOD mice efficiently induced type 1 diabetes (T1D). Following disease induction IL-22-producing Teff17 cells could be recovered from the islets of recipient NOD mice. However, neutralizing anti-IL-22 antibody therapy did not prevent the adoptive transfer of disease by the polarized Teff17 cells. This indicated other factors beside IL-22 contributed to disease. We found polarized Teff17 cell supernatant containing IL-17 and IL-22 induced the expression of regenerating (Reg) genes in pancreatic islets in vitro. The role of IL-17 and IL-22 was further confirmed by the induction of Reg genes in the islets by low dose of the recombinant IL-17 and IL-22 in vitro. Reg genes have been implicated in the islet regeneration and we recently showed an increased islet β-cell DNA synthesis in vitro in the presence of IL-22 (Cell Regen. 2013;2(2):1-11). Our studies therefore suggest cytokines produced by Th17 cells have a dose-dependent immunomodulatory role in islet protection and regeneration in T1D.
(Studies in our laboratory are supported by Canadian Institutes of Health Research)