| First Author | Nowarski R | Year | 2015 |
| Journal | Cell | Volume | 163 |
| Issue | 6 | Pages | 1444-56 |
| PubMed ID | 26638073 | Mgi Jnum | J:227990 |
| Mgi Id | MGI:5704236 | Doi | 10.1016/j.cell.2015.10.072 |
| Citation | Nowarski R, et al. (2015) Epithelial IL-18 Equilibrium Controls Barrier Function in Colitis. Cell 163(6):1444-56 |
| abstractText | 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 (Delta/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(Delta/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. |
