Abstract
We have shown that pathogenic T helper type 17 (Th17) cells differentiated from naive CD4(+) T cells of BDC2·5 T cell receptor transgenic non-obese diabetic (NOD) mice by interleukin (IL)-23 plus IL-6 produce IL-17, IL-22 and induce type 1 diabetes (T1D). Neutralizing interferon (IFN)-γ during the polarization process leads to a significant increase in IL-22 production by these Th17 cells. We also isolated IL-22-producing Th17 cells from the pancreas of wild-type diabetic NOD mice. IL-27 also blocked IL-22 production from diabetogenic Th17 cells. To determine the functional role of IL-22 produced by pathogenic Th17 cells in T1D we neutralized IL-22 in vivo by using anti-IL-22 monoclonal antibody. We found that blocking IL-22 did not alter significantly adoptive transfer of disease by pathogenic Th17 cells. Therefore, IL-22 is not required for T1D pathogenesis. The IL-22Rα receptor for IL-22 however, increased in the pancreas of NOD mice during disease progression and based upon our and other studies we suggest that IL-22 may have a regenerative and protective role in the pancreatic islets.