Th17-cell plasticity in Helicobacter hepaticus –induced intestinal inflammation

Top of pageAbstract 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.