Mice deficient in IL-25 are less susceptible to dextran sulfate sodium-induced colitis (P3270)

Abstract

Abstract IL-25 is a member of IL-17 cytokine family and is highly expressed in gastrointestinal epithelial cells. The biological activities of IL-25 have been associated with promotion of Th2 but inhibition of Th1/Th17 immunity. Whether IL-25 plays a role in the development of colonic inflammation is unresolved. In this study, we investigated the contribution of IL-25 to DSS-induced colitis in mice. C57BL/6 WT and IL-25-/- mice received 3% DSS in the drinking water ad libitum and were euthanized eight days later. When compared to WT mice, IL-25-/- mice lost significantly less body weight and had delayed appearance of diarrhea and bloody stool, as well as less shortened colon length. Histological evaluation of H&E-stained tissue sections of colon showed that IL-25-/- mice had only mild inflammation, while severe inflammation developed in WT mice based on the extent of focal crypt lesions, loss of goblet cells, and infiltration of inflammatory cells. IL-33 purportedly contributes to intestinal inflammation and qPCR analysis of colonic cytokine expression showed an up-regulation of IL-33 in DSS-treated WT but not IL-25-/- mice. In addition, there were significantly fewer transcripts of the pro-inflammatory cytokines (TNFα, IL-6, IL-17A) in the colon of DSS-treated IL-25-/- than WT mice. Overall, these data suggested that a deficiency in IL-25 partially protected mice from DSS-induced colitis, revealing a previously unidentified pro-inflammatory role for IL-25 in colonic inflammation.