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Intestinal-epithelial LSD1 controls goblet cell maturation and effector responses required for gut immunity to bacterial and helminth infection
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 regulator...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041206/ https://www.ncbi.nlm.nih.gov/pubmed/33788902 http://dx.doi.org/10.1371/journal.ppat.1009476 |
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author | Parmar, Naveen Burrows, Kyle Vornewald, Pia M. Lindholm, Håvard T. Zwiggelaar, Rosalie T. Díez-Sánchez, Alberto Martín-Alonso, Mara Fosslie, Madeleine Vallance, Bruce A. Dahl, John Arne Zaph, Colby Oudhoff, Menno J. |
author_facet | Parmar, Naveen Burrows, Kyle Vornewald, Pia M. Lindholm, Håvard T. Zwiggelaar, Rosalie T. Díez-Sánchez, Alberto Martín-Alonso, Mara Fosslie, Madeleine Vallance, Bruce A. Dahl, John Arne Zaph, Colby Oudhoff, Menno J. |
author_sort | Parmar, Naveen |
collection | PubMed |
description | 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 RELMß. 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. |
format | Online Article Text |
id | pubmed-8041206 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-80412062021-04-20 Intestinal-epithelial LSD1 controls goblet cell maturation and effector responses required for gut immunity to bacterial and helminth infection Parmar, Naveen Burrows, Kyle Vornewald, Pia M. Lindholm, Håvard T. Zwiggelaar, Rosalie T. Díez-Sánchez, Alberto Martín-Alonso, Mara Fosslie, Madeleine Vallance, Bruce A. Dahl, John Arne Zaph, Colby Oudhoff, Menno J. PLoS Pathog Research Article 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 RELMß. 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. Public Library of Science 2021-03-31 /pmc/articles/PMC8041206/ /pubmed/33788902 http://dx.doi.org/10.1371/journal.ppat.1009476 Text en © 2021 Parmar et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Parmar, Naveen Burrows, Kyle Vornewald, Pia M. Lindholm, Håvard T. Zwiggelaar, Rosalie T. Díez-Sánchez, Alberto Martín-Alonso, Mara Fosslie, Madeleine Vallance, Bruce A. Dahl, John Arne Zaph, Colby Oudhoff, Menno J. Intestinal-epithelial LSD1 controls goblet cell maturation and effector responses required for gut immunity to bacterial and helminth infection |
title | Intestinal-epithelial LSD1 controls goblet cell maturation and effector responses required for gut immunity to bacterial and helminth infection |
title_full | Intestinal-epithelial LSD1 controls goblet cell maturation and effector responses required for gut immunity to bacterial and helminth infection |
title_fullStr | Intestinal-epithelial LSD1 controls goblet cell maturation and effector responses required for gut immunity to bacterial and helminth infection |
title_full_unstemmed | Intestinal-epithelial LSD1 controls goblet cell maturation and effector responses required for gut immunity to bacterial and helminth infection |
title_short | Intestinal-epithelial LSD1 controls goblet cell maturation and effector responses required for gut immunity to bacterial and helminth infection |
title_sort | intestinal-epithelial lsd1 controls goblet cell maturation and effector responses required for gut immunity to bacterial and helminth infection |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041206/ https://www.ncbi.nlm.nih.gov/pubmed/33788902 http://dx.doi.org/10.1371/journal.ppat.1009476 |
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