IL-27 regulates homeostasis of the intestinal CD4⁺ effector T cell pool and limits intestinal inflammation in a murine model of colitis

IL-27 limits CD4⁺ T_H17 cell development in vitro and during inflammatory responses in the CNS. However, whether IL-27-IL-27R interactions regulate the homeostasis or function of CD4⁺ T cell populations in the intestine is unknown. To test this, we examined CD4 ⁺ T cell populations in the intestine of wild-type and IL-27R ^-/- mice. Naive IL-27R^-/- mice exhibited a selective decrease in the frequency of IFN-γ producing CD4⁺ T _H1 cells and an increase in the frequency of T_H17 cells in gut-associated lymphoid tissues. Associated with elevated expression of IL-17A, IL-27R^-/- mice exhibited earlier onset and significantly increased severity of clinical disease compared with wild-type controls in a murine model of intestinal inflammation. Rag^-/-/IL-27R^-/- mice were also more susceptible than Rag^-/- mice to development of dextran sodium sulfate-induced intestinal inflammation, indicating an additional role for IL-27-IL-27R in the regulation of innate immune cell function. Consistent with this, IL-27 inhibited proinflammatory cytokine production by activated neutrophils. Collectively, these data identify a role for IL-27-IL-27R interaction in controlling the homeostasis of the intestinal T cell pool and in limiting intestinal inflammation through regulation of innate and adaptive immune cell function.