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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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
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.
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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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