@article{7522f2f714e14448bb1083eb1d7dbe6f,
title = "Intestinal-epithelial LSD1 controls goblet cell maturation and effector responses required for gut immunity to bacterial and helminth infection",
abstract = "Infectious and inflammatory diseases in the intestine remain a serious threat for patients world-wide. Reprogramming of the intestinal epithelium towards a protective effector state is important to manage inflammation and immunity and can be therapeutically targeted. The role of epigenetic regulatory enzymes within these processes is not yet defined. Here, we use a mouse model that has an intestinal-epithelial specific deletion of the histone demethylase Lsd1 (cKO mice), which maintains the epithelium in a fixed reparative state. Challenge of cKO mice with bacteria-induced colitis or a helminth infection model both resulted in increased pathogenesis. Mechanistically, we discovered that LSD1 is important for goblet cell maturation and goblet-cell effector molecules such as RELM{\ss}. We propose that this may be in part mediated by directly controlling genes that facilitate cytoskeletal organization, which is important in goblet cell biology. This study therefore identifies intestinal-epithelial epigenetic regulation by LSD1 as a critical element in host protection from infection.",
author = "Naveen Parmar and Kyle Burrows and Vornewald, {Pia M.} and Lindholm, {H{\aa}vard T.} and Zwiggelaar, {Rosalie T.} and Alberto D{\'i}ez-S{\'a}nchez and Mara Mart{\'i}n-Alonso and Madeleine Fosslie and Vallance, {Bruce A.} and Dahl, {John Arne} and Colby Zaph and Oudhoff, {Menno J.}",
note = "Funding Information: This work was provided by the Norwegian Research Council (Centre of Excellence grant 223255/F50, and 'Young Research Talent' 274760 to MJO) and the Norwegian Cancer Society (182767 to MJO). MMA is the recipient of a Marie Sk{\l}odowska-Curie IF (DLV-794391). This work was also supported by the South-Eastern Norway Regional Health Authority, Early Career Grant 2016058, and the Research Council of Norway “Young Research Talent” grant to JAD. KB is a Banting Fellow. MF is supported by the Norwegian Research Council (grant no. 275286). CZ is supported by the Australian National Health and Medical Research Council (APP1104433 and APP1104466). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank Drs. Stuart Orkin and Sylvie Robine for kindly sharing mouse strains. We thank the imaging (CMIC), genomics (GCF), and animal care (CoMed) core facilities that assisted in this work (NTNU). BAV is the CH.I.L.D. Foundation Chair in Pediatric Gastroenterology. Publisher Copyright: {\textcopyright} 2021 Parmar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.",
year = "2021",
month = mar,
day = "31",
doi = "10.1371/JOURNAL.PPAT.1009476",
language = "English",
volume = "17",
journal = "PLoS Pathogens",
issn = "1553-7366",
publisher = "Public Library of Science (PLoS)",
number = "3",
}