IL-18Rα-deficient CD4+T cells induce intestinal inflammation in the CD45RBhitransfer model of colitis despite impaired innate responsiveness

Petra Holmkvist, Lieneke Pool, Karin Hägerbrand, William Winston Agace, Aymeric Marie Christian Rivollier

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    IL-18 has been implicated in inflammatory bowel disease (IBD), however its role in the regulation of intestinal CD4+ T-cell function remains unclear. Here we show that murine intestinal CD4+ T cells express high levels of IL-18Rα and provide evidence that IL-18Rα expression is induced on these cells subsequent to their entry into the intestinal mucosa. Using the CD45RBhi T-cell transfer colitis model, we show that IL-18Rα is expressed on IFN-γ+, IL-17+ and IL-17+IFN-γ+ effector CD4+ T cells in the inflamed colonic lamina propria (cLP) and mesenteric lymph node (MLN) and is required for the optimal generation and/or maintenance of IFN-γ-producing cells in the cLP. In the steady state and during colitis, TCR-independent cytokine-induced IFN-γ and IL-17 production by intestinal CD4+ T cells was largely IL-18Rα−dependent. Despite these findings however, IL-18Rα−deficient CD4+ T cells induced comparable intestinal pathology to WT CD4+ T cells. These findings suggest that IL-18-dependent cytokine induced activation of CD4+ T cells is not critical for the development of T-cell-mediated colitis.
    Original languageEnglish
    JournalEuropean Journal of Immunology
    Issue number6
    Pages (from-to)1371-1382
    Publication statusPublished - 2016

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