IL-18Rα-deficient CD4+ T cells induce intestinal inflammation in the CD45RBhi 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-18R alpha and provide evidence that IL-18Ra 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-18R alpha is expressed on IFN-gamma(+), IL-17(+), and IL-17(+)IFN-gamma(+) 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-gamma-producing cells in the cLP. In the steady state and during colitis, TCR-independent cytokine-induced IFN-gamma and IL-17 production by intestinal CD4(+) T cells was largely IL-18R alpha-dependent. Despite these findings however, IL-18R alpha-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.