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Th17-cell plasticity in Helicobacter hepaticus-induced intestinal inflammation.
- Source :
-
Mucosal immunology [Mucosal Immunol] 2013 Nov; Vol. 6 (6), pp. 1143-56. Date of Electronic Publication: 2013 Mar 06. - Publication Year :
- 2013
-
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.
- Subjects :
- Animals
Cells, Cultured
Colitis etiology
Helicobacter Infections complications
Humans
Inflammation microbiology
Interferon-gamma metabolism
Interleukin-10 genetics
Interleukin-10 metabolism
Interleukin-17 metabolism
Interleukin-23 metabolism
Mice, Inbred C57BL
Mice, Knockout
Organ Culture Techniques
Typhlitis etiology
Colitis immunology
Helicobacter Infections immunology
Helicobacter hepaticus immunology
Intestines immunology
Th1 Cells immunology
Th17 Cells immunology
Typhlitis immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1935-3456
- Volume :
- 6
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Mucosal immunology
- Publication Type :
- Academic Journal
- Accession number :
- 23462910
- Full Text :
- https://doi.org/10.1038/mi.2013.11