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Epithelial IL-18 Equilibrium Controls Barrier Function in Colitis
Open accessAbstract
SUMMARY 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−/−;Il18rΔ/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 which underlies the pathology of Ulcerative Colitis.
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Metadata
- Authors
- Nowarski, R., Jackson, R., Gagliani, N., de Zoete, M. R., Palm, N. W., Bailis, W., Low, J. S., Harman, C. C. D., Graham, M., Elinav, E., & Flavell, R. A.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2015-12
- Volume
- 163
- Issue
- 6
- Pages
- 1444-1456
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2184709292
- Cited by
- 558
- References
- 10
- FWCI
- 21.79
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Nowarski, R., Jackson, R., Gagliani, N., de Zoete, M. R., Palm, N. W., Bailis, W., Low, J. S., Harman, C. C. D., Graham, M., Elinav, E., & Flavell, R. A. (2015). Epithelial IL-18 Equilibrium Controls Barrier Function in Colitis. Cell. https://doi.org/10.1016/j.cell.2015.10.072
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