Cdx2 regulates immune cell infiltration in the intestine

Abstract The intestinal epithelium is a unique tissue, serving both as a barrier against pathogens and to conduct the end digestion and adsorption of nutrients. As regards the former, the intestinal epithelium contains a diverse repertoire of immune cells, including a variety of resident lymphocytes...

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Autores principales:	Simon Chewchuk, Sanzida Jahan, David Lohnes
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5b6048e8dbe447e7bb434ad5d9ee67dd
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spelling	oai:doaj.org-article:5b6048e8dbe447e7bb434ad5d9ee67dd2021-12-02T14:53:42ZCdx2 regulates immune cell infiltration in the intestine10.1038/s41598-021-95412-w2045-2322https://doaj.org/article/5b6048e8dbe447e7bb434ad5d9ee67dd2021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-95412-whttps://doaj.org/toc/2045-2322Abstract The intestinal epithelium is a unique tissue, serving both as a barrier against pathogens and to conduct the end digestion and adsorption of nutrients. As regards the former, the intestinal epithelium contains a diverse repertoire of immune cells, including a variety of resident lymphocytes, macrophages and dendritic cells. These cells serve a number of roles including mitigation of infection and to stimulate regeneration in response to damage. The transcription factor Cdx2, and to a lesser extent Cdx1, plays essential roles in intestinal homeostasis, and acts as a context-dependent tumour suppressor in colorectal cancer. Deletion of Cdx2 from the murine intestinal epithelium leads to macrophage infiltration resulting in a chronic inflammatory response. However the mechanisms by which Cdx2 loss evokes this response are poorly understood. To better understand this relationship, we used a conditional mouse model lacking all intestinal Cdx function to identify potential target genes which may contribute to this inflammatory phenotype. One such candidate encodes the histocompatability complex protein H2-T3, which functions to regulate intestinal iCD8α lymphocyte activity. We found that Cdx2 occupies the H3-T3 promoter in vivo and directly regulates its expression via a Cdx response element. Loss of Cdx function leads to a rapid and pronounced attenuation of H2-T3, followed by a decrease in iCD8α cell number, an increase in macrophage infiltration and activation of pro-inflammatory cascades. These findings suggest a previously unrecognized role for Cdx in intestinal homeostasis through H2-T3-dependent regulation of iCD8α cells.Simon ChewchukSanzida JahanDavid LohnesNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Simon Chewchuk Sanzida Jahan David Lohnes Cdx2 regulates immune cell infiltration in the intestine
description	Abstract The intestinal epithelium is a unique tissue, serving both as a barrier against pathogens and to conduct the end digestion and adsorption of nutrients. As regards the former, the intestinal epithelium contains a diverse repertoire of immune cells, including a variety of resident lymphocytes, macrophages and dendritic cells. These cells serve a number of roles including mitigation of infection and to stimulate regeneration in response to damage. The transcription factor Cdx2, and to a lesser extent Cdx1, plays essential roles in intestinal homeostasis, and acts as a context-dependent tumour suppressor in colorectal cancer. Deletion of Cdx2 from the murine intestinal epithelium leads to macrophage infiltration resulting in a chronic inflammatory response. However the mechanisms by which Cdx2 loss evokes this response are poorly understood. To better understand this relationship, we used a conditional mouse model lacking all intestinal Cdx function to identify potential target genes which may contribute to this inflammatory phenotype. One such candidate encodes the histocompatability complex protein H2-T3, which functions to regulate intestinal iCD8α lymphocyte activity. We found that Cdx2 occupies the H3-T3 promoter in vivo and directly regulates its expression via a Cdx response element. Loss of Cdx function leads to a rapid and pronounced attenuation of H2-T3, followed by a decrease in iCD8α cell number, an increase in macrophage infiltration and activation of pro-inflammatory cascades. These findings suggest a previously unrecognized role for Cdx in intestinal homeostasis through H2-T3-dependent regulation of iCD8α cells.
format	article
author	Simon Chewchuk Sanzida Jahan David Lohnes
author_facet	Simon Chewchuk Sanzida Jahan David Lohnes
author_sort	Simon Chewchuk
title	Cdx2 regulates immune cell infiltration in the intestine
title_short	Cdx2 regulates immune cell infiltration in the intestine
title_full	Cdx2 regulates immune cell infiltration in the intestine
title_fullStr	Cdx2 regulates immune cell infiltration in the intestine
title_full_unstemmed	Cdx2 regulates immune cell infiltration in the intestine
title_sort	cdx2 regulates immune cell infiltration in the intestine
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/5b6048e8dbe447e7bb434ad5d9ee67dd
work_keys_str_mv	AT simonchewchuk cdx2regulatesimmunecellinfiltrationintheintestine AT sanzidajahan cdx2regulatesimmunecellinfiltrationintheintestine AT davidlohnes cdx2regulatesimmunecellinfiltrationintheintestine
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Cdx2 regulates immune cell infiltration in the intestine

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