IL-18Rα-deficient CD4+ T cells induce intestinal inflammation in the CD45RBhi transfer model of colitis despite impaired innate responsiveness

Research output: Contribution to journalArticle


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.


External organisations
  • Technical University of Denmark
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Immunology in the medical area


  • IFN-γ, IL-18 receptor signaling, Innate responsiveness, T-cell transfer colitis
Original languageEnglish
Pages (from-to)1371-1382
Number of pages12
JournalEuropean Journal of Immunology
Issue number6
Publication statusPublished - 2016 Jun 1
Publication categoryResearch