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

ABSTRACT: 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. Genome-wide transcription factors mapping and binding of STAT3, H3K4me3, H3K27me, H3K4me1, H3K27ac in mouse CD4+ T cells and dendritic cells in WT and Stat3-/- mice. RNA-Seq is performed in mouse CD4+ T cells and dendritic cells in WT mice, with or without indicated cytokines.

ORGANISM(S): Mus musculus

SUBMITTER: Warren J Leonard Peng Li Allison B Andraski Chi-Keung Wan Rosanne Spolski Jangsuk Oh Christopher P Dillon Zu-Xi Yu Ning Du Douglas R Green

PROVIDER: E-GEOD-61677 | ArrayExpress | 2015-08-19

SECONDARY ACCESSION(S): GSE61677SRP047424PRJNA261817

REPOSITORIES: GEO, ArrayExpress, ENA

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