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NEMO Prevents RIP Kinase 1-Mediated Epithelial Cell Death and Chronic Intestinal Inflammation by NF-κB-Dependent and -Independent Functions
Intestinal epithelial cells (IECs) regulate gut immune homeostasis, and impaired epithelial responses are implicated in the pathogenesis of inflammatory bowel diseases (IBD). IEC-specific ablation of nuclear factor κB (NF-κB) essential modulator (NEMO) caused Paneth cell apoptosis and impaired antim...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cell Press
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4803910/ https://www.ncbi.nlm.nih.gov/pubmed/26982364 http://dx.doi.org/10.1016/j.immuni.2016.02.020 |
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author | Vlantis, Katerina Wullaert, Andy Polykratis, Apostolos Kondylis, Vangelis Dannappel, Marius Schwarzer, Robin Welz, Patrick Corona, Teresa Walczak, Henning Weih, Falk Klein, Ulf Kelliher, Michelle Pasparakis, Manolis |
author_facet | Vlantis, Katerina Wullaert, Andy Polykratis, Apostolos Kondylis, Vangelis Dannappel, Marius Schwarzer, Robin Welz, Patrick Corona, Teresa Walczak, Henning Weih, Falk Klein, Ulf Kelliher, Michelle Pasparakis, Manolis |
author_sort | Vlantis, Katerina |
collection | PubMed |
description | Intestinal epithelial cells (IECs) regulate gut immune homeostasis, and impaired epithelial responses are implicated in the pathogenesis of inflammatory bowel diseases (IBD). IEC-specific ablation of nuclear factor κB (NF-κB) essential modulator (NEMO) caused Paneth cell apoptosis and impaired antimicrobial factor expression in the ileum, as well as colonocyte apoptosis and microbiota-driven chronic inflammation in the colon. Combined RelA, c-Rel, and RelB deficiency in IECs caused Paneth cell apoptosis but not colitis, suggesting that NEMO prevents colon inflammation by NF-κB-independent functions. Inhibition of receptor-interacting protein kinase 1 (RIPK1) kinase activity or combined deficiency of Fas-associated via death domain protein (FADD) and RIPK3 prevented epithelial cell death, Paneth cell loss, and colitis development in mice with epithelial NEMO deficiency. Therefore, NEMO prevents intestinal inflammation by inhibiting RIPK1 kinase activity-mediated IEC death, suggesting that RIPK1 inhibitors could be effective in the treatment of colitis in patients with NEMO mutations and possibly in IBD. |
format | Online Article Text |
id | pubmed-4803910 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Cell Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-48039102016-04-06 NEMO Prevents RIP Kinase 1-Mediated Epithelial Cell Death and Chronic Intestinal Inflammation by NF-κB-Dependent and -Independent Functions Vlantis, Katerina Wullaert, Andy Polykratis, Apostolos Kondylis, Vangelis Dannappel, Marius Schwarzer, Robin Welz, Patrick Corona, Teresa Walczak, Henning Weih, Falk Klein, Ulf Kelliher, Michelle Pasparakis, Manolis Immunity Article Intestinal epithelial cells (IECs) regulate gut immune homeostasis, and impaired epithelial responses are implicated in the pathogenesis of inflammatory bowel diseases (IBD). IEC-specific ablation of nuclear factor κB (NF-κB) essential modulator (NEMO) caused Paneth cell apoptosis and impaired antimicrobial factor expression in the ileum, as well as colonocyte apoptosis and microbiota-driven chronic inflammation in the colon. Combined RelA, c-Rel, and RelB deficiency in IECs caused Paneth cell apoptosis but not colitis, suggesting that NEMO prevents colon inflammation by NF-κB-independent functions. Inhibition of receptor-interacting protein kinase 1 (RIPK1) kinase activity or combined deficiency of Fas-associated via death domain protein (FADD) and RIPK3 prevented epithelial cell death, Paneth cell loss, and colitis development in mice with epithelial NEMO deficiency. Therefore, NEMO prevents intestinal inflammation by inhibiting RIPK1 kinase activity-mediated IEC death, suggesting that RIPK1 inhibitors could be effective in the treatment of colitis in patients with NEMO mutations and possibly in IBD. Cell Press 2016-03-15 /pmc/articles/PMC4803910/ /pubmed/26982364 http://dx.doi.org/10.1016/j.immuni.2016.02.020 Text en © 2016 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Vlantis, Katerina Wullaert, Andy Polykratis, Apostolos Kondylis, Vangelis Dannappel, Marius Schwarzer, Robin Welz, Patrick Corona, Teresa Walczak, Henning Weih, Falk Klein, Ulf Kelliher, Michelle Pasparakis, Manolis NEMO Prevents RIP Kinase 1-Mediated Epithelial Cell Death and Chronic Intestinal Inflammation by NF-κB-Dependent and -Independent Functions |
title | NEMO Prevents RIP Kinase 1-Mediated Epithelial Cell Death and Chronic Intestinal Inflammation by NF-κB-Dependent and -Independent Functions |
title_full | NEMO Prevents RIP Kinase 1-Mediated Epithelial Cell Death and Chronic Intestinal Inflammation by NF-κB-Dependent and -Independent Functions |
title_fullStr | NEMO Prevents RIP Kinase 1-Mediated Epithelial Cell Death and Chronic Intestinal Inflammation by NF-κB-Dependent and -Independent Functions |
title_full_unstemmed | NEMO Prevents RIP Kinase 1-Mediated Epithelial Cell Death and Chronic Intestinal Inflammation by NF-κB-Dependent and -Independent Functions |
title_short | NEMO Prevents RIP Kinase 1-Mediated Epithelial Cell Death and Chronic Intestinal Inflammation by NF-κB-Dependent and -Independent Functions |
title_sort | nemo prevents rip kinase 1-mediated epithelial cell death and chronic intestinal inflammation by nf-κb-dependent and -independent functions |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4803910/ https://www.ncbi.nlm.nih.gov/pubmed/26982364 http://dx.doi.org/10.1016/j.immuni.2016.02.020 |
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