GSE61677
IL-21-mediated non-canonical pathway for IL-1ß production in conventional dendritic cells
The canonical pathway for IL-1ß production requires TLR-mediated NF-?B-dependent Il1b gene induction, followed by caspase-containing inflammasome-mediated processing of pro-IL-1ß.  Here we show that IL-21 unexpectedly induces IL-1ß 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-1ß 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-1ß 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-1ß via a non-canonical pathway and provide evidence for its importance in vivo. Overall design: 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.