Th17-cell plasticity in Helicobacter hepaticus-induced intestinal inflammation

Research output: Contribution to journalArticle

Authors

  • P J Morrison
  • L A Fouser
  • J F Wright
  • B Stockinger
  • A Cooke
  • M C Kullberg

Colleges, School and Institutes

External organisations

  • Centre for Immunology and Infection, Department of Biology and Hull York Medical School, University of York, York, UK.

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.

Details

Original languageEnglish
Pages (from-to)1143-56
Number of pages14
JournalMucosal immunology
Volume6
Issue number6
Publication statusPublished - Nov 2013

Keywords

  • Animals, Cells, Cultured, Colitis, Helicobacter Infections, Helicobacter hepaticus, Humans, Inflammation, Interferon-gamma, Interleukin-10, Interleukin-17, Interleukin-23, Intestines, Mice, Inbred C57BL, Mice, Knockout, Organ Culture Techniques, Th1 Cells, Th17 Cells, Typhlitis, Journal Article, Research Support, Non-U.S. Gov't