A Role for IL-27/IL-27R Signaling in Prevention of Acute Intestinal Inflammation (B53)

IL-27 is a member of the IL-12 cytokine family initially implicated in promoting Th1 cell differentiation. IL-27 is elevated in the intestines of inflammatory bowel disease patients and in a murine model of this disease, although the influence of IL-27 on intestinal inflammation remains unclear. To address this, we employed IL-27R−/− mice and the dextran sodium sulfate (DSS) model of acute intestinal inflammation. Following exposure to 5% DSS, IL-27R−/− mice exhibited early and severe disease, as defined by increased weight loss, increased severity of edema and inflammatory lesions in the colon, and increased diarrhea and intestinal bleeding. This pathology lead to high mortality in IL-27R−/− mice during the first five days of DSS treatment. Cytokines IL-6 and IL-17 were elevated in IL-27R−/− mice, while other pro-inflammatory cytokines such as IFNγ remained unchanged. IL-17 was produced both by CD4+ T cells and by non-T cells. Finally, the lamina propria of DSS-treated IL-27R−/− mice contained increased frequencies of innate immune cells following treatment. These results indicate that endogenous IL-27-IL-27R signaling can regulate both innate and adaptive immune cells and contribute to prevention of severe intestinal inflammation.