Th17-cell plasticity in Helicobacter hepaticus–induced intestinal inflammation

Bacterial-induced intestinal inflammation is crucially dependent on interleukin (IL)-23 and is associated with CD4 + T helper type 1 (Th1) and Th17 responses. However, the relative contributions of these subsets during the induction and resolution of colitis in T-cell-sufficient hosts remain unknown. We report that Helicobacter hepaticus –induced typhlocolitis in specific pathogen-free IL-10 −/− mice is associated with elevated frequencies and numbers of large intestinal interferon (IFN)-γ + and IFN-γ + IL-17A + CD4 + T cells. By assessing histone modifications and transcript levels in IFN-γ + , IFN-γ + IL-17A + , and IL-17A + CD4 + T cells isolated from the inflamed intestine, we show that Th17 cells are predisposed to upregulate the Th1 program and that they express IL-23R but not IL-12R. Using IL-17A fate-reporter mice, we further demonstrate that H. hepaticus infection gives rise to Th17 cells that extinguish IL-17A secretion and turn on IFN-γ within 10 days post bacterial inoculation. Together, our results suggest that bacterial-induced Th17 cells arising in disease-susceptible hosts contribute to intestinal pathology by switching phenotype, transitioning via an IFN-γ + IL-17A + stage, to become IFN-γ + ex-Th17 cells.