Pluto Bioinformatics

GSE61677: IL-21-mediated non-canonical pathway for IL-1 production in conventional dendritic cells

Bulk RNA sequencing

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. SOURCE: Peng Li (peng.li@nih.gov) - LMI NIH