title: Th17-cell plasticity in Helicobacter hepaticus-induced intestinal inflammation.
abstract: 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.
authors: Centre for Immunology and Infection, Department of Biology and Hull York Medical School, University of York, York, UK.
authors: P J
authors: PJ
authors: Morrison
authors: D
authors: D
authors: Bending
authors: L A
authors: LA
authors: Fouser
authors: J F
authors: JF
authors: Wright
authors: B
authors: B
authors: Stockinger
authors: A
authors: A
authors: Cooke
authors: M C
authors: MC
authors: Kullberg
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003092:Colitis / Q000209:etiology / Q000276:immunology*; D016481:Helicobacter Infections / Q000150:complications / Q000276:immunology*; D044923:Helicobacter hepaticus / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000382:microbiology; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D053759:Interleukin-23 / Q000378:metabolism; D007422:Intestines / Q000276:immunology*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009924:Organ Culture Techniques; D018417:Th1 Cells / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*; D053706:Typhlitis / Q000209:etiology / Q000276:immunology*
chemical_list: D020381:Interleukin-17; D053759:Interleukin-23; D016753:Interleukin-10; D007371:Interferon-gamma