Cargando…
Transcriptional regulation of the Th17 immune response by IKKα
Th17 cells are a subset of T cells that play crucial roles in the pathogenesis of many inflammatory diseases. We report here the identification of IKKα (inhibitor of NF-κB kinase-α) as a key transcriptional regulator of the Th17 lineage. T cells expressing a nonactivatable form of IKKα were signific...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2011
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3135338/ https://www.ncbi.nlm.nih.gov/pubmed/21402739 http://dx.doi.org/10.1084/jem.20091346 |
_version_ | 1782208086754197504 |
---|---|
author | Li, Li Ruan, Qingguo Hilliard, Brendan DeVirgiliis, Jennifer Karin, Michael Chen, Youhai H. |
author_facet | Li, Li Ruan, Qingguo Hilliard, Brendan DeVirgiliis, Jennifer Karin, Michael Chen, Youhai H. |
author_sort | Li, Li |
collection | PubMed |
description | Th17 cells are a subset of T cells that play crucial roles in the pathogenesis of many inflammatory diseases. We report here the identification of IKKα (inhibitor of NF-κB kinase-α) as a key transcriptional regulator of the Th17 lineage. T cells expressing a nonactivatable form of IKKα were significantly compromised in their ability to produce IL-17 and to initiate neural inflammation. IKKα is present in the nuclei of resting CD4(+) T cells. Upon Th17 differentiation, IKKα selectively associated with the Il17a locus, and promoted its histone H3 phosphorylation and transcriptional activation in a NF-κB–independent manner. These findings indicate that nuclear IKKα maintains the Th17 phenotype by activating the Il17a gene. |
format | Online Article Text |
id | pubmed-3135338 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-31353382011-10-11 Transcriptional regulation of the Th17 immune response by IKKα Li, Li Ruan, Qingguo Hilliard, Brendan DeVirgiliis, Jennifer Karin, Michael Chen, Youhai H. J Exp Med Article Th17 cells are a subset of T cells that play crucial roles in the pathogenesis of many inflammatory diseases. We report here the identification of IKKα (inhibitor of NF-κB kinase-α) as a key transcriptional regulator of the Th17 lineage. T cells expressing a nonactivatable form of IKKα were significantly compromised in their ability to produce IL-17 and to initiate neural inflammation. IKKα is present in the nuclei of resting CD4(+) T cells. Upon Th17 differentiation, IKKα selectively associated with the Il17a locus, and promoted its histone H3 phosphorylation and transcriptional activation in a NF-κB–independent manner. These findings indicate that nuclear IKKα maintains the Th17 phenotype by activating the Il17a gene. The Rockefeller University Press 2011-04-11 /pmc/articles/PMC3135338/ /pubmed/21402739 http://dx.doi.org/10.1084/jem.20091346 Text en © 2011 Li et al. 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 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Article Li, Li Ruan, Qingguo Hilliard, Brendan DeVirgiliis, Jennifer Karin, Michael Chen, Youhai H. Transcriptional regulation of the Th17 immune response by IKKα |
title | Transcriptional regulation of the Th17 immune response by IKKα |
title_full | Transcriptional regulation of the Th17 immune response by IKKα |
title_fullStr | Transcriptional regulation of the Th17 immune response by IKKα |
title_full_unstemmed | Transcriptional regulation of the Th17 immune response by IKKα |
title_short | Transcriptional regulation of the Th17 immune response by IKKα |
title_sort | transcriptional regulation of the th17 immune response by ikkα |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3135338/ https://www.ncbi.nlm.nih.gov/pubmed/21402739 http://dx.doi.org/10.1084/jem.20091346 |
work_keys_str_mv | AT lili transcriptionalregulationoftheth17immuneresponsebyikka AT ruanqingguo transcriptionalregulationoftheth17immuneresponsebyikka AT hilliardbrendan transcriptionalregulationoftheth17immuneresponsebyikka AT devirgiliisjennifer transcriptionalregulationoftheth17immuneresponsebyikka AT karinmichael transcriptionalregulationoftheth17immuneresponsebyikka AT chenyouhaih transcriptionalregulationoftheth17immuneresponsebyikka |