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IκBζ controls IL-17-triggered gene expression program in intestinal epithelial cells that restricts colonization of SFB and prevents Th17-associated pathologies
Control of gut microbes is crucial for not only local defense in the intestine but also proper systemic immune responses. Although intestinal epithelial cells (IECs) play important roles in cytokine-mediated control of enterobacteria, the underlying mechanisms are not fully understood. Here we show...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group US
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9705257/ https://www.ncbi.nlm.nih.gov/pubmed/35999460 http://dx.doi.org/10.1038/s41385-022-00554-3 |
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author | Yamazaki, Soh Inohara, Naohiro Ohmuraya, Masaki Tsuneoka, Yousuke Yagita, Hideo Katagiri, Takaharu Nishina, Takashi Mikami, Tetuo Funato, Hiromasa Araki, Kimi Nakano, Hiroyasu |
author_facet | Yamazaki, Soh Inohara, Naohiro Ohmuraya, Masaki Tsuneoka, Yousuke Yagita, Hideo Katagiri, Takaharu Nishina, Takashi Mikami, Tetuo Funato, Hiromasa Araki, Kimi Nakano, Hiroyasu |
author_sort | Yamazaki, Soh |
collection | PubMed |
description | Control of gut microbes is crucial for not only local defense in the intestine but also proper systemic immune responses. Although intestinal epithelial cells (IECs) play important roles in cytokine-mediated control of enterobacteria, the underlying mechanisms are not fully understood. Here we show that deletion of IκBζ in IECs in mice leads to dysbiosis with marked expansion of segmented filamentous bacteria (SFB), thereby enhancing Th17 cell development and exacerbating inflammatory diseases. Mechanistically, the IκBζ deficiency results in decrease in the number of Paneth cells and impairment in expression of IL-17-inducible genes involved in IgA production. The decrease in Paneth cells is caused by aberrant activation of IFN-γ signaling and a failure of IL-17-dependent recovery from IFN-γ-induced damage. Thus, the IL-17R–IκBζ axis in IECs contributes to the maintenance of intestinal homeostasis by serving as a key component in a regulatory loop between the gut microbiota and immune cells. |
format | Online Article Text |
id | pubmed-9705257 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group US |
record_format | MEDLINE/PubMed |
spelling | pubmed-97052572022-11-30 IκBζ controls IL-17-triggered gene expression program in intestinal epithelial cells that restricts colonization of SFB and prevents Th17-associated pathologies Yamazaki, Soh Inohara, Naohiro Ohmuraya, Masaki Tsuneoka, Yousuke Yagita, Hideo Katagiri, Takaharu Nishina, Takashi Mikami, Tetuo Funato, Hiromasa Araki, Kimi Nakano, Hiroyasu Mucosal Immunol Article Control of gut microbes is crucial for not only local defense in the intestine but also proper systemic immune responses. Although intestinal epithelial cells (IECs) play important roles in cytokine-mediated control of enterobacteria, the underlying mechanisms are not fully understood. Here we show that deletion of IκBζ in IECs in mice leads to dysbiosis with marked expansion of segmented filamentous bacteria (SFB), thereby enhancing Th17 cell development and exacerbating inflammatory diseases. Mechanistically, the IκBζ deficiency results in decrease in the number of Paneth cells and impairment in expression of IL-17-inducible genes involved in IgA production. The decrease in Paneth cells is caused by aberrant activation of IFN-γ signaling and a failure of IL-17-dependent recovery from IFN-γ-induced damage. Thus, the IL-17R–IκBζ axis in IECs contributes to the maintenance of intestinal homeostasis by serving as a key component in a regulatory loop between the gut microbiota and immune cells. Nature Publishing Group US 2022-08-24 2022 /pmc/articles/PMC9705257/ /pubmed/35999460 http://dx.doi.org/10.1038/s41385-022-00554-3 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Yamazaki, Soh Inohara, Naohiro Ohmuraya, Masaki Tsuneoka, Yousuke Yagita, Hideo Katagiri, Takaharu Nishina, Takashi Mikami, Tetuo Funato, Hiromasa Araki, Kimi Nakano, Hiroyasu IκBζ controls IL-17-triggered gene expression program in intestinal epithelial cells that restricts colonization of SFB and prevents Th17-associated pathologies |
title | IκBζ controls IL-17-triggered gene expression program in intestinal epithelial cells that restricts colonization of SFB and prevents Th17-associated pathologies |
title_full | IκBζ controls IL-17-triggered gene expression program in intestinal epithelial cells that restricts colonization of SFB and prevents Th17-associated pathologies |
title_fullStr | IκBζ controls IL-17-triggered gene expression program in intestinal epithelial cells that restricts colonization of SFB and prevents Th17-associated pathologies |
title_full_unstemmed | IκBζ controls IL-17-triggered gene expression program in intestinal epithelial cells that restricts colonization of SFB and prevents Th17-associated pathologies |
title_short | IκBζ controls IL-17-triggered gene expression program in intestinal epithelial cells that restricts colonization of SFB and prevents Th17-associated pathologies |
title_sort | iκbζ controls il-17-triggered gene expression program in intestinal epithelial cells that restricts colonization of sfb and prevents th17-associated pathologies |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9705257/ https://www.ncbi.nlm.nih.gov/pubmed/35999460 http://dx.doi.org/10.1038/s41385-022-00554-3 |
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