Altered Mucus Barrier Integrity and Increased Susceptibility to Colitis in Mice upon Loss of Telocyte Bone Morphogenetic Protein Signalling

FoxL1+-Telocytes (TCFoxL1+) are subepithelial cells that form a network underneath the epithelium. We have shown that without inflammatory stress, mice with loss of function in the BMP signalling pathway in TCFoxL1+ (BmpR1...

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Autores principales:	Vilcy Reyes Nicolás, Joannie M. Allaire, Alain B. Alfonso, Dianne Pupo Gómez, Véronique Pomerleau, Véronique Giroux, François Boudreau, Nathalie Perreault
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	inflammatory bowel diseases cellular microenvironment wound healing goblet cells <i>O</i>-glycosylation Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/30890b31f2f24b6eaf282b4bf92e143a
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spelling	oai:doaj.org-article:30890b31f2f24b6eaf282b4bf92e143a2021-11-25T17:09:46ZAltered Mucus Barrier Integrity and Increased Susceptibility to Colitis in Mice upon Loss of Telocyte Bone Morphogenetic Protein Signalling10.3390/cells101129542073-4409https://doaj.org/article/30890b31f2f24b6eaf282b4bf92e143a2021-10-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/2954https://doaj.org/toc/2073-4409FoxL1<sup>+</sup>-Telocytes (TC<sup>FoxL1+</sup>) are subepithelial cells that form a network underneath the epithelium. We have shown that without inflammatory stress, mice with loss of function in the BMP signalling pathway in TC<sup>FoxL1+</sup> (<i>BmpR1a</i><sup>ΔFoxL1+</sup>) initiated colonic neoplasia. Although TC<sup>FoxL1+</sup> are modulated in IBD patients, their specific role in this pathogenesis remains unclear. Thus, we investigated how the loss of BMP signalling in TC<sup>FoxL1+</sup> influences the severity of inflammation and fosters epithelial recovery after inflammatory stress. <i>BmpR1a</i> was genetically ablated in mouse colonic TC<sup>FoxL1+</sup>. Experimental colitis was performed using a DSS challenge followed by recovery steps to assess wound healing. Physical barrier properties, including mucus composition and glycosylation, were assessed by alcian blue staining, immunofluorescences and RT-qPCR. We found that <i>BmpR1a</i><sup>ΔFoxL1+</sup> mice had impaired mucus quality, and upon exposure to inflammatory challenges, they had increased susceptibility to experimental colitis and delayed healing. In addition, defective BMP signalling in TC<sup>FoxL1+</sup> altered the functionality of goblet cells, thereby affecting mucosal structure and promoting bacterial invasion. Following inflammatory stress, TC<sup>FoxL1+</sup> with impaired BMP signalling lose their homing signal for optimal distribution along the epithelium, which is critical in tissue regeneration after injury. Overall, our findings revealed key roles of BMP signalling in TC<sup>FoxL1+</sup> in IBD pathogenesis.Vilcy Reyes NicolásJoannie M. AllaireAlain B. AlfonsoDianne Pupo GómezVéronique PomerleauVéronique GirouxFrançois BoudreauNathalie PerreaultMDPI AGarticleinflammatory bowel diseasescellular microenvironmentwound healinggoblet cells<i>O</i>-glycosylationBiology (General)QH301-705.5ENCells, Vol 10, Iss 2954, p 2954 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	inflammatory bowel diseases cellular microenvironment wound healing goblet cells <i>O</i>-glycosylation Biology (General) QH301-705.5
spellingShingle	inflammatory bowel diseases cellular microenvironment wound healing goblet cells <i>O</i>-glycosylation Biology (General) QH301-705.5 Vilcy Reyes Nicolás Joannie M. Allaire Alain B. Alfonso Dianne Pupo Gómez Véronique Pomerleau Véronique Giroux François Boudreau Nathalie Perreault Altered Mucus Barrier Integrity and Increased Susceptibility to Colitis in Mice upon Loss of Telocyte Bone Morphogenetic Protein Signalling
description	FoxL1<sup>+</sup>-Telocytes (TC<sup>FoxL1+</sup>) are subepithelial cells that form a network underneath the epithelium. We have shown that without inflammatory stress, mice with loss of function in the BMP signalling pathway in TC<sup>FoxL1+</sup> (<i>BmpR1a</i><sup>ΔFoxL1+</sup>) initiated colonic neoplasia. Although TC<sup>FoxL1+</sup> are modulated in IBD patients, their specific role in this pathogenesis remains unclear. Thus, we investigated how the loss of BMP signalling in TC<sup>FoxL1+</sup> influences the severity of inflammation and fosters epithelial recovery after inflammatory stress. <i>BmpR1a</i> was genetically ablated in mouse colonic TC<sup>FoxL1+</sup>. Experimental colitis was performed using a DSS challenge followed by recovery steps to assess wound healing. Physical barrier properties, including mucus composition and glycosylation, were assessed by alcian blue staining, immunofluorescences and RT-qPCR. We found that <i>BmpR1a</i><sup>ΔFoxL1+</sup> mice had impaired mucus quality, and upon exposure to inflammatory challenges, they had increased susceptibility to experimental colitis and delayed healing. In addition, defective BMP signalling in TC<sup>FoxL1+</sup> altered the functionality of goblet cells, thereby affecting mucosal structure and promoting bacterial invasion. Following inflammatory stress, TC<sup>FoxL1+</sup> with impaired BMP signalling lose their homing signal for optimal distribution along the epithelium, which is critical in tissue regeneration after injury. Overall, our findings revealed key roles of BMP signalling in TC<sup>FoxL1+</sup> in IBD pathogenesis.
format	article
author	Vilcy Reyes Nicolás Joannie M. Allaire Alain B. Alfonso Dianne Pupo Gómez Véronique Pomerleau Véronique Giroux François Boudreau Nathalie Perreault
author_facet	Vilcy Reyes Nicolás Joannie M. Allaire Alain B. Alfonso Dianne Pupo Gómez Véronique Pomerleau Véronique Giroux François Boudreau Nathalie Perreault
author_sort	Vilcy Reyes Nicolás
title	Altered Mucus Barrier Integrity and Increased Susceptibility to Colitis in Mice upon Loss of Telocyte Bone Morphogenetic Protein Signalling
title_short	Altered Mucus Barrier Integrity and Increased Susceptibility to Colitis in Mice upon Loss of Telocyte Bone Morphogenetic Protein Signalling
title_full	Altered Mucus Barrier Integrity and Increased Susceptibility to Colitis in Mice upon Loss of Telocyte Bone Morphogenetic Protein Signalling
title_fullStr	Altered Mucus Barrier Integrity and Increased Susceptibility to Colitis in Mice upon Loss of Telocyte Bone Morphogenetic Protein Signalling
title_full_unstemmed	Altered Mucus Barrier Integrity and Increased Susceptibility to Colitis in Mice upon Loss of Telocyte Bone Morphogenetic Protein Signalling
title_sort	altered mucus barrier integrity and increased susceptibility to colitis in mice upon loss of telocyte bone morphogenetic protein signalling
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/30890b31f2f24b6eaf282b4bf92e143a
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Altered Mucus Barrier Integrity and Increased Susceptibility to Colitis in Mice upon Loss of Telocyte Bone Morphogenetic Protein Signalling

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