| Literature DB >> 26638073 |
Roni Nowarski1, Ruaidhrí Jackson1, Nicola Gagliani1, Marcel R de Zoete1, Noah W Palm1, Will Bailis1, Jun Siong Low1, Christian C D Harman1, Morven Graham2, Eran Elinav3, Richard A Flavell4.
Abstract
The intestinal mucosal barrier controlling the resident microbiome is dependent on a protective mucus layer generated by goblet cells, impairment of which is a hallmark of the inflammatory bowel disease, ulcerative colitis. Here, we show that IL-18 is critical in driving the pathologic breakdown of barrier integrity in a model of colitis. Deletion of Il18 or its receptor Il18r1 in intestinal epithelial cells (Δ/EC) conferred protection from colitis and mucosal damage in mice. In contrast, deletion of the IL-18 negative regulator Il18bp resulted in severe colitis associated with loss of mature goblet cells. Colitis and goblet cell loss were rescued in Il18bp(-/-);Il18r(Δ/EC) mice, demonstrating that colitis severity is controlled at the level of IL-18 signaling in intestinal epithelial cells. IL-18 inhibited goblet cell maturation by regulating the transcriptional program instructing goblet cell development. These results inform on the mechanism of goblet cell dysfunction that underlies the pathology of ulcerative colitis.Entities:
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Year: 2015 PMID： 26638073 PMCID： PMC4943028 DOI： 10.1016/j.cell.2015.10.072
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582