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Guidance of super-enhancers in regulation of IL-9 induction and airway inflammation
Th9 cells are prominently featured in allergic lung inflammation, but the mechanism that regulates IL-9 induction in T helper cells remains poorly defined. Here we demonstrate that formation of super-enhancers (SEs) is critical in robust induction of IL-9 and that assembly of the Il9 SEs in Th cells...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5789412/ https://www.ncbi.nlm.nih.gov/pubmed/29339447 http://dx.doi.org/10.1084/jem.20170928 |
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author | Xiao, Xiang Fan, Yihui Li, Junhui Zhang, Xiaolong Lou, Xiaohua Dou, Yaling Shi, Xiaomin Lan, Peixiang Xiao, Yue Minze, Laurie Li, Xian Chang |
author_facet | Xiao, Xiang Fan, Yihui Li, Junhui Zhang, Xiaolong Lou, Xiaohua Dou, Yaling Shi, Xiaomin Lan, Peixiang Xiao, Yue Minze, Laurie Li, Xian Chang |
author_sort | Xiao, Xiang |
collection | PubMed |
description | Th9 cells are prominently featured in allergic lung inflammation, but the mechanism that regulates IL-9 induction in T helper cells remains poorly defined. Here we demonstrate that formation of super-enhancers (SEs) is critical in robust induction of IL-9 and that assembly of the Il9 SEs in Th cells requires OX40-triggered chromatin acetylation. Mechanistically, we found that OX40 costimulation induces RelB expression, which recruits the histone acetyltransferase p300 to the Il9 locus to catalyze H3K27 acetylation. This allows binding of the SE factor Brd4 to organize assembly of the SE complex, which in turn drives robust IL-9 expression and Th9 cell induction. Thus, Th9 cells are strongly induced upon OX40 stimulation, and disruption of SEs abolished Th9 cell induction in vitro and inhibited Th9 cell–mediated allergic airway inflammation in vivo. Together, our data suggest that formation of SEs is essential in IL-9 expression and Th9 cell induction. These findings may have important clinical implications. |
format | Online Article Text |
id | pubmed-5789412 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-57894122018-08-05 Guidance of super-enhancers in regulation of IL-9 induction and airway inflammation Xiao, Xiang Fan, Yihui Li, Junhui Zhang, Xiaolong Lou, Xiaohua Dou, Yaling Shi, Xiaomin Lan, Peixiang Xiao, Yue Minze, Laurie Li, Xian Chang J Exp Med Research Articles Th9 cells are prominently featured in allergic lung inflammation, but the mechanism that regulates IL-9 induction in T helper cells remains poorly defined. Here we demonstrate that formation of super-enhancers (SEs) is critical in robust induction of IL-9 and that assembly of the Il9 SEs in Th cells requires OX40-triggered chromatin acetylation. Mechanistically, we found that OX40 costimulation induces RelB expression, which recruits the histone acetyltransferase p300 to the Il9 locus to catalyze H3K27 acetylation. This allows binding of the SE factor Brd4 to organize assembly of the SE complex, which in turn drives robust IL-9 expression and Th9 cell induction. Thus, Th9 cells are strongly induced upon OX40 stimulation, and disruption of SEs abolished Th9 cell induction in vitro and inhibited Th9 cell–mediated allergic airway inflammation in vivo. Together, our data suggest that formation of SEs is essential in IL-9 expression and Th9 cell induction. These findings may have important clinical implications. The Rockefeller University Press 2018-02-05 /pmc/articles/PMC5789412/ /pubmed/29339447 http://dx.doi.org/10.1084/jem.20170928 Text en © 2018 Xiao et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Research Articles Xiao, Xiang Fan, Yihui Li, Junhui Zhang, Xiaolong Lou, Xiaohua Dou, Yaling Shi, Xiaomin Lan, Peixiang Xiao, Yue Minze, Laurie Li, Xian Chang Guidance of super-enhancers in regulation of IL-9 induction and airway inflammation |
title | Guidance of super-enhancers in regulation of IL-9 induction and airway inflammation |
title_full | Guidance of super-enhancers in regulation of IL-9 induction and airway inflammation |
title_fullStr | Guidance of super-enhancers in regulation of IL-9 induction and airway inflammation |
title_full_unstemmed | Guidance of super-enhancers in regulation of IL-9 induction and airway inflammation |
title_short | Guidance of super-enhancers in regulation of IL-9 induction and airway inflammation |
title_sort | guidance of super-enhancers in regulation of il-9 induction and airway inflammation |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5789412/ https://www.ncbi.nlm.nih.gov/pubmed/29339447 http://dx.doi.org/10.1084/jem.20170928 |
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