IL-18Rα-deficient CD4(+) T cells induce intestinal inflammation in the CD45RB(hi) transfer model of colitis despite impaired innate responsiveness.

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 CD45RB(hi) 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.