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IL-21-mediated non-canonical pathway for IL-1β production in conventional dendritic cells
The canonical pathway for IL-1β production requires TLR-mediated NF-κB-dependent Il1b gene induction, followed by caspase-containing inflammasome-mediated processing of pro-IL-1β. Here we show that IL-21 unexpectedly induces IL-1β production in conventional dendritic cells (cDCs) via a STAT3-depende...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Pub. Group
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4555999/ https://www.ncbi.nlm.nih.gov/pubmed/26269257 http://dx.doi.org/10.1038/ncomms8988 |
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author | Wan, Chi-Keung Li, Peng Spolski, Rosanne Oh, Jangsuk Andraski, Allison B. Du, Ning Yu, Zu-Xi Dillon, Christopher P. Green, Douglas R. Leonard, Warren J. |
author_facet | Wan, Chi-Keung Li, Peng Spolski, Rosanne Oh, Jangsuk Andraski, Allison B. Du, Ning Yu, Zu-Xi Dillon, Christopher P. Green, Douglas R. Leonard, Warren J. |
author_sort | Wan, Chi-Keung |
collection | PubMed |
description | The canonical pathway for IL-1β production requires TLR-mediated NF-κB-dependent Il1b gene induction, followed by caspase-containing inflammasome-mediated processing of pro-IL-1β. Here we show that IL-21 unexpectedly induces IL-1β production in conventional dendritic cells (cDCs) via a STAT3-dependent but NF-κB-independent pathway. IL-21 does not induce Il1b expression in CD4(+) T cells, with differential histone marks present in these cells versus cDCs. IL-21-induced IL-1β processing in cDCs does not require caspase-1 or caspase-8 but depends on IL-21-mediated death and activation of serine protease(s). Moreover, STAT3-dependent IL-1β expression in cDCs at least partially explains the IL-21-mediated pathologic response occurring during infection with pneumonia virus of mice. These results demonstrate lineage-restricted IL-21-induced IL-1β via a non-canonical pathway and provide evidence for its importance in vivo. |
format | Online Article Text |
id | pubmed-4555999 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Pub. Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-45559992015-09-14 IL-21-mediated non-canonical pathway for IL-1β production in conventional dendritic cells Wan, Chi-Keung Li, Peng Spolski, Rosanne Oh, Jangsuk Andraski, Allison B. Du, Ning Yu, Zu-Xi Dillon, Christopher P. Green, Douglas R. Leonard, Warren J. Nat Commun Article The canonical pathway for IL-1β production requires TLR-mediated NF-κB-dependent Il1b gene induction, followed by caspase-containing inflammasome-mediated processing of pro-IL-1β. Here we show that IL-21 unexpectedly induces IL-1β production in conventional dendritic cells (cDCs) via a STAT3-dependent but NF-κB-independent pathway. IL-21 does not induce Il1b expression in CD4(+) T cells, with differential histone marks present in these cells versus cDCs. IL-21-induced IL-1β processing in cDCs does not require caspase-1 or caspase-8 but depends on IL-21-mediated death and activation of serine protease(s). Moreover, STAT3-dependent IL-1β expression in cDCs at least partially explains the IL-21-mediated pathologic response occurring during infection with pneumonia virus of mice. These results demonstrate lineage-restricted IL-21-induced IL-1β via a non-canonical pathway and provide evidence for its importance in vivo. Nature Pub. Group 2015-08-13 /pmc/articles/PMC4555999/ /pubmed/26269257 http://dx.doi.org/10.1038/ncomms8988 Text en Copyright © 2015, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Wan, Chi-Keung Li, Peng Spolski, Rosanne Oh, Jangsuk Andraski, Allison B. Du, Ning Yu, Zu-Xi Dillon, Christopher P. Green, Douglas R. Leonard, Warren J. IL-21-mediated non-canonical pathway for IL-1β production in conventional dendritic cells |
title | IL-21-mediated non-canonical pathway for IL-1β production in conventional dendritic cells |
title_full | IL-21-mediated non-canonical pathway for IL-1β production in conventional dendritic cells |
title_fullStr | IL-21-mediated non-canonical pathway for IL-1β production in conventional dendritic cells |
title_full_unstemmed | IL-21-mediated non-canonical pathway for IL-1β production in conventional dendritic cells |
title_short | IL-21-mediated non-canonical pathway for IL-1β production in conventional dendritic cells |
title_sort | il-21-mediated non-canonical pathway for il-1β production in conventional dendritic cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4555999/ https://www.ncbi.nlm.nih.gov/pubmed/26269257 http://dx.doi.org/10.1038/ncomms8988 |
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