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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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-08-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-95412-w |
| _version_ | 1818682465135362048 |
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| author | Simon Chewchuk Sanzida Jahan David Lohnes |
| author_facet | Simon Chewchuk Sanzida Jahan David Lohnes |
| author_sort | Simon Chewchuk |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-17T10:19:16Z |
| format | Article |
| id | doaj.art-5b6048e8dbe447e7bb434ad5d9ee67dd |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-17T10:19:16Z |
| publishDate | 2021-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-5b6048e8dbe447e7bb434ad5d9ee67dd2022-12-21T21:52:50ZengNature PortfolioScientific Reports2045-23222021-08-0111111210.1038/s41598-021-95412-wCdx2 regulates immune cell infiltration in the intestineSimon Chewchuk0Sanzida Jahan1David Lohnes2Department of Cellular and Molecular Medicine, University of OttawaDepartment of Cellular and Molecular Medicine, University of OttawaDepartment of Cellular and Molecular Medicine, University of OttawaAbstract 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.https://doi.org/10.1038/s41598-021-95412-w |
| spellingShingle | Simon Chewchuk Sanzida Jahan David Lohnes Cdx2 regulates immune cell infiltration in the intestine Scientific Reports |
| title | 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_short | Cdx2 regulates immune cell infiltration in the intestine |
| title_sort | cdx2 regulates immune cell infiltration in the intestine |
| url | https://doi.org/10.1038/s41598-021-95412-w |
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