IL-21-mediated Non-canonical Pathway for IL-1β Production in Conventional Dendritic Cells

Overview

Journal Nat Commun

Specialty Biology

Date 2015 Aug 14

PMID 26269257

Citations 12

Authors

Chi-Keung Wan

Peng Li

Rosanne Spolski

Jangsuk Oh

Allison B Andraski

Ning Du

Zu-Xi Yu

Christopher P Dillon

Douglas R Green

Warren J Leonard

Affiliations

Soon will be listed here.

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.

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