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IL-21-mediated non-canonical pathway for IL-1? production in conventional dendritic cells.


ABSTRACT: The canonical pathway for IL-1? production requires TLR-mediated NF-?B-dependent Il1b gene induction, followed by caspase-containing inflammasome-mediated processing of pro-IL-1?. Here we show that IL-21 unexpectedly induces IL-1? production in conventional dendritic cells (cDCs) via a STAT3-dependent but NF-?B-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-1? 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-1? 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-1? via a non-canonical pathway and provide evidence for its importance in vivo.

SUBMITTER: Wan CK 

PROVIDER: S-EPMC4555999 | BioStudies | 2015-01-01

REPOSITORIES: biostudies

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