IL-21-mediated non-canonical pathway for IL-1[beta] 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...

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Bibliographic Details
Published in:Nature communications 2015-08, Vol.6, p.7988
Main Authors: 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
Format: Article
Language:English
Subjects:
Caspase
Caspase-1
Caspase-8
CD4 antigen
Dendritic cells
IL-1β
Inflammasomes
Interleukin 1
Interleukin 21
Lymphocytes
Lymphocytes T
NF-κB protein
Serine
Serine proteinase
Stat3 protein
Viruses
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Summary: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.
ISSN:2041-1723
DOI:10.1038/ncomms8988