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Epithelial IL-18 Equilibrium Controls Barrier Function in Colitis

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Epithelial IL-18 Equilibrium Controls Barrier Function in Colitis. / Nowarski, Roni; Jackson, Ruaidhrí; Gagliani, Nicola; de Zoete, Marcel R; Palm, Noah W; Bailis, Will; Low, Jun Siong; Harman, Christian C D; Graham, Morven; Elinav, Eran; Flavell, Richard A.

in: CELL, Jahrgang 163, Nr. 6, 03.12.2015, S. 1444-56.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Nowarski, R, Jackson, R, Gagliani, N, de Zoete, MR, Palm, NW, Bailis, W, Low, JS, Harman, CCD, Graham, M, Elinav, E & Flavell, RA 2015, 'Epithelial IL-18 Equilibrium Controls Barrier Function in Colitis', CELL, Jg. 163, Nr. 6, S. 1444-56. https://doi.org/10.1016/j.cell.2015.10.072

APA

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, 163(6), 1444-56. https://doi.org/10.1016/j.cell.2015.10.072

Vancouver

Nowarski R, Jackson R, Gagliani N, de Zoete MR, Palm NW, Bailis W et al. Epithelial IL-18 Equilibrium Controls Barrier Function in Colitis. CELL. 2015 Dez 3;163(6):1444-56. https://doi.org/10.1016/j.cell.2015.10.072

Bibtex

@article{c88f59484031481197b1e6c6b30a5650,
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 (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.",
keywords = "Animals, Colitis, Ulcerative, Dextran Sulfate, Endothelial Cells, Epithelial Cells, Female, Goblet Cells, Intercellular Signaling Peptides and Proteins, Interleukin-18, Interleukin-18 Receptor alpha Subunit, Intestinal Mucosa, Male, Mice, Signal Transduction, Journal Article, Research Support, Non-U.S. Gov't",
author = "Roni Nowarski and Ruaidhr{\'i} 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 = "Copyright {\textcopyright} 2015 Elsevier Inc. All rights reserved.",
year = "2015",
month = dec,
day = "3",
doi = "10.1016/j.cell.2015.10.072",
language = "English",
volume = "163",
pages = "1444--56",
journal = "CELL",
issn = "0092-8674",
publisher = "Cell Press",
number = "6",

}

RIS

TY - JOUR

T1 - Epithelial IL-18 Equilibrium Controls Barrier Function in Colitis

AU - Nowarski, Roni

AU - Jackson, Ruaidhrí

AU - Gagliani, Nicola

AU - de Zoete, Marcel R

AU - Palm, Noah W

AU - Bailis, Will

AU - Low, Jun Siong

AU - Harman, Christian C D

AU - Graham, Morven

AU - Elinav, Eran

AU - Flavell, Richard A

N1 - Copyright © 2015 Elsevier Inc. All rights reserved.

PY - 2015/12/3

Y1 - 2015/12/3

N2 - 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.

AB - 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.

KW - Animals

KW - Colitis, Ulcerative

KW - Dextran Sulfate

KW - Endothelial Cells

KW - Epithelial Cells

KW - Female

KW - Goblet Cells

KW - Intercellular Signaling Peptides and Proteins

KW - Interleukin-18

KW - Interleukin-18 Receptor alpha Subunit

KW - Intestinal Mucosa

KW - Male

KW - Mice

KW - Signal Transduction

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/j.cell.2015.10.072

DO - 10.1016/j.cell.2015.10.072

M3 - SCORING: Journal article

C2 - 26638073

VL - 163

SP - 1444

EP - 1456

JO - CELL

JF - CELL

SN - 0092-8674

IS - 6

ER -