@article{d6d93768bc64498baa7df56f787bcd30,
title = "Epithelial IL-18 Equilibrium Controls Barrier Function in Colitis",
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 (D/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.",
author = "Roni Nowarski and Ruaidhri Jackson and Nicola Gagliani and {de Zoete}, {Marcel R.} and Palm, {Noah W.} and Will Bailis and Low, {Jun Siong} and Harman, {Christian C. D.} and Morven Graham and Eran Elinav and Flavell, {Richard A.}",
note = "We would like to thank Caroline Lieber, Judith Stein, Jon Alderman, Cindy Hughes, and Elizabeth Hughes-Picard for technical assistance. N.G. is sup-ported by the Dr. Keith Landesman Memorial Fellowship of the Cancer Research Institute, M.R.d.Z. is supported by a Rubicon Fellowship from the Netherlands Organization of Scientific Research, N.W.P. and W.B. are sup-ported by the Cancer Research Institute Irvington Fellowship Program,C.C.D.H. is supported by a Howard Hughes Medical Institute International Student Research Fellowship, and R.N. is supported by the Jane Coffin Childs Fund Postdoctoral Fellowship. This work was supported in part by the Howard Hughes Medical Institute and the Blavatnik Family Foundation (R.A.F.). AUTHOR CONTRIBUTIONS R.N. and R.J. conceived, performed, and analyzed the experiments and wrote the manuscript. N.G., M.R.d.Z., N.W.P., W.B., J.S.L., C.C.D.H., M.G., and E.E.provided technical assistance in various experiments. R.A.F. supervised the project and participated in interpreting the results and writing the manuscript.",
year = "2015",
month = dec,
day = "6",
doi = "https://doi.org/10.1016/j.cell.2015.10.072",
language = "الإنجليزيّة",
volume = "163",
pages = "1444--1456",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "6",
}