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.