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KLF5 protects the intestinal epithelium against Th17 immune response in a murine colitis model
Inflammatory bowel disease (IBD) is a chronic illness characterized by dysregulated immune cascades in the intestines, in which the Th17 immune response plays an important role. We demonstrated that mice with intestinal epithelium–specific deletion of Krüppel-like factor 5 (Klf5) developed Th17-depe...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Clinical Investigation
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9057631/ https://www.ncbi.nlm.nih.gov/pubmed/35393949 http://dx.doi.org/10.1172/jci.insight.153488 |
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author | Shieh, Jason Chu, Timothy H. Liu, Yang Kim, Julie Ruiz de Sabando, Ainara Kobayashi, Soma Zee, Sui Y. Sheridan, Brian S. Bialkowska, Agnieszka B. Yang, Vincent W. |
author_facet | Shieh, Jason Chu, Timothy H. Liu, Yang Kim, Julie Ruiz de Sabando, Ainara Kobayashi, Soma Zee, Sui Y. Sheridan, Brian S. Bialkowska, Agnieszka B. Yang, Vincent W. |
author_sort | Shieh, Jason |
collection | PubMed |
description | Inflammatory bowel disease (IBD) is a chronic illness characterized by dysregulated immune cascades in the intestines, in which the Th17 immune response plays an important role. We demonstrated that mice with intestinal epithelium–specific deletion of Krüppel-like factor 5 (Klf5) developed Th17-dependent colonic inflammation. In the absence of KLF5, there was aberrant cellular localization of phosphorylated STAT3, an essential mediator of the Th17-associated cytokine, IL-22, which is required for epithelial tissue regeneration. In contrast, mitigation of IL-17A with anti–IL-17A neutralizing antibody attenuated colitis in Klf5-deficient mice. There was also a considerable shift in the colonic microbiota of Klf5-deficient mice that phenocopied human IBD. Notably, the inflammatory response due to Klf5 deletion was alleviated by antibiotic treatment, implicating the role of microbiota in pathogenesis. Finally, human colitic tissues had reduced KLF5 levels when compared with healthy tissues. Together, these findings demonstrated the importance of KLF5 in protecting the intestinal epithelium against Th17-mediated immune and inflammatory responses. The mice described herein may serve as a potential model for human IBD. |
format | Online Article Text |
id | pubmed-9057631 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Society for Clinical Investigation |
record_format | MEDLINE/PubMed |
spelling | pubmed-90576312022-05-04 KLF5 protects the intestinal epithelium against Th17 immune response in a murine colitis model Shieh, Jason Chu, Timothy H. Liu, Yang Kim, Julie Ruiz de Sabando, Ainara Kobayashi, Soma Zee, Sui Y. Sheridan, Brian S. Bialkowska, Agnieszka B. Yang, Vincent W. JCI Insight Research Article Inflammatory bowel disease (IBD) is a chronic illness characterized by dysregulated immune cascades in the intestines, in which the Th17 immune response plays an important role. We demonstrated that mice with intestinal epithelium–specific deletion of Krüppel-like factor 5 (Klf5) developed Th17-dependent colonic inflammation. In the absence of KLF5, there was aberrant cellular localization of phosphorylated STAT3, an essential mediator of the Th17-associated cytokine, IL-22, which is required for epithelial tissue regeneration. In contrast, mitigation of IL-17A with anti–IL-17A neutralizing antibody attenuated colitis in Klf5-deficient mice. There was also a considerable shift in the colonic microbiota of Klf5-deficient mice that phenocopied human IBD. Notably, the inflammatory response due to Klf5 deletion was alleviated by antibiotic treatment, implicating the role of microbiota in pathogenesis. Finally, human colitic tissues had reduced KLF5 levels when compared with healthy tissues. Together, these findings demonstrated the importance of KLF5 in protecting the intestinal epithelium against Th17-mediated immune and inflammatory responses. The mice described herein may serve as a potential model for human IBD. American Society for Clinical Investigation 2022-04-08 /pmc/articles/PMC9057631/ /pubmed/35393949 http://dx.doi.org/10.1172/jci.insight.153488 Text en © 2022 Shieh et al. https://creativecommons.org/licenses/by/4.0/This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Article Shieh, Jason Chu, Timothy H. Liu, Yang Kim, Julie Ruiz de Sabando, Ainara Kobayashi, Soma Zee, Sui Y. Sheridan, Brian S. Bialkowska, Agnieszka B. Yang, Vincent W. KLF5 protects the intestinal epithelium against Th17 immune response in a murine colitis model |
title | KLF5 protects the intestinal epithelium against Th17 immune response in a murine colitis model |
title_full | KLF5 protects the intestinal epithelium against Th17 immune response in a murine colitis model |
title_fullStr | KLF5 protects the intestinal epithelium against Th17 immune response in a murine colitis model |
title_full_unstemmed | KLF5 protects the intestinal epithelium against Th17 immune response in a murine colitis model |
title_short | KLF5 protects the intestinal epithelium against Th17 immune response in a murine colitis model |
title_sort | klf5 protects the intestinal epithelium against th17 immune response in a murine colitis model |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9057631/ https://www.ncbi.nlm.nih.gov/pubmed/35393949 http://dx.doi.org/10.1172/jci.insight.153488 |
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