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POH1 deubiquitinates pro-interleukin-1β and restricts inflammasome activity
Inflammasome activation is essential for host defence against invading pathogens, but is also involved in various forms of inflammatory diseases. The processes that control inflammasome activity are thus important for averting excessive immune responses and tissue damage. Here we show that the deubi...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6185913/ https://www.ncbi.nlm.nih.gov/pubmed/30315153 http://dx.doi.org/10.1038/s41467-018-06455-z |
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author | Zhang, Li Liu, Yun Wang, Boshi Xu, Guiqin Yang, Zhaojuan Tang, Ming Ma, Aihui Jing, Tiantian Xu, Xiaoli Zhang, Xiaoren Liu, Yongzhong |
author_facet | Zhang, Li Liu, Yun Wang, Boshi Xu, Guiqin Yang, Zhaojuan Tang, Ming Ma, Aihui Jing, Tiantian Xu, Xiaoli Zhang, Xiaoren Liu, Yongzhong |
author_sort | Zhang, Li |
collection | PubMed |
description | Inflammasome activation is essential for host defence against invading pathogens, but is also involved in various forms of inflammatory diseases. The processes that control inflammasome activity are thus important for averting excessive immune responses and tissue damage. Here we show that the deubiquitinase POH1 negatively regulates the immune response triggered by inflammasome activation. POH1 deficiency in macrophages enhances mature IL-1β production without significant alterations in inflammasome priming and ASC-caspase-1 activation. In WT macrophages, POH1 interacts with and deubiquitinates pro-IL-1β by decreasing the K63-linked polyubiquitin chains, as well as decreases the efficacy of pro-IL-1β cleavage. Furthermore, myeloid cell-specific deletion of POH1 aggravates lipopolysaccharide-induced systemic inflammation and alum-induced peritonitis inflammatory responses in vivo. Our study thereby reveals that POH1-mediated deubiquitination of pro-IL-1β is an important regulatory event that restrains inflammatory responses for the maintenance of immune homeostasis. |
format | Online Article Text |
id | pubmed-6185913 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-61859132018-10-15 POH1 deubiquitinates pro-interleukin-1β and restricts inflammasome activity Zhang, Li Liu, Yun Wang, Boshi Xu, Guiqin Yang, Zhaojuan Tang, Ming Ma, Aihui Jing, Tiantian Xu, Xiaoli Zhang, Xiaoren Liu, Yongzhong Nat Commun Article Inflammasome activation is essential for host defence against invading pathogens, but is also involved in various forms of inflammatory diseases. The processes that control inflammasome activity are thus important for averting excessive immune responses and tissue damage. Here we show that the deubiquitinase POH1 negatively regulates the immune response triggered by inflammasome activation. POH1 deficiency in macrophages enhances mature IL-1β production without significant alterations in inflammasome priming and ASC-caspase-1 activation. In WT macrophages, POH1 interacts with and deubiquitinates pro-IL-1β by decreasing the K63-linked polyubiquitin chains, as well as decreases the efficacy of pro-IL-1β cleavage. Furthermore, myeloid cell-specific deletion of POH1 aggravates lipopolysaccharide-induced systemic inflammation and alum-induced peritonitis inflammatory responses in vivo. Our study thereby reveals that POH1-mediated deubiquitination of pro-IL-1β is an important regulatory event that restrains inflammatory responses for the maintenance of immune homeostasis. Nature Publishing Group UK 2018-10-12 /pmc/articles/PMC6185913/ /pubmed/30315153 http://dx.doi.org/10.1038/s41467-018-06455-z Text en © The Author(s) 2018 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/. |
spellingShingle | Article Zhang, Li Liu, Yun Wang, Boshi Xu, Guiqin Yang, Zhaojuan Tang, Ming Ma, Aihui Jing, Tiantian Xu, Xiaoli Zhang, Xiaoren Liu, Yongzhong POH1 deubiquitinates pro-interleukin-1β and restricts inflammasome activity |
title | POH1 deubiquitinates pro-interleukin-1β and restricts inflammasome activity |
title_full | POH1 deubiquitinates pro-interleukin-1β and restricts inflammasome activity |
title_fullStr | POH1 deubiquitinates pro-interleukin-1β and restricts inflammasome activity |
title_full_unstemmed | POH1 deubiquitinates pro-interleukin-1β and restricts inflammasome activity |
title_short | POH1 deubiquitinates pro-interleukin-1β and restricts inflammasome activity |
title_sort | poh1 deubiquitinates pro-interleukin-1β and restricts inflammasome activity |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6185913/ https://www.ncbi.nlm.nih.gov/pubmed/30315153 http://dx.doi.org/10.1038/s41467-018-06455-z |
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