Th17-cell plasticity in Helicobacter hepaticus-induced intestinal inflammation
Th17-cell plasticity in Helicobacter hepaticus-induced intestinal inflammation
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DOI：
10.1038/mi.2013.11
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发表时间：
2013-11-01
影响因子：
8
通讯作者：
Kullberg, M. C.
中科院分区：
文献类型：
--
作者：
Morrison, P. J.;Bending, D.;Kullberg, M. C.
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)-gamma(+) and IFN--gamma+IL-17A(+) CD4(+) T cells. By assessing histone modifications and transcript levels in IFN-gamma(+), IFN-gamma+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-gamma 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-gamma+IL-17A(+) stage, to become IFN-gamma(+) ex-Th17 cells.
