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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...

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Detalles Bibliográficos
Autores principales: Li, Li, Ruan, Qingguo, Hilliard, Brendan, DeVirgiliis, Jennifer, Karin, Michael, Chen, Youhai H.
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
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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.
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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
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