Prdx4 limits caspase-1 activation and restricts inflammasome-mediated signaling by extracellular vesicles

ABSTRACT: Inflammasomes are cytosolic protein complexes, which orchestrate the maturation of active IL 1b by proteolytic cleavage via caspase-1. Although many principles of inflammasome activation have been described, mechanisms that limit inflammasome-dependent immune responses remain poorly defined. Here, we show that the thiol-specific peroxidase Peroxiredoxin-4 (Prdx4) directly regulates IL 1b generation by interfering with caspase-1 activity. We demonstrate that caspase-1 and Prdx4 form a redox-sensitive regulatory complex via caspase-1 cysteine 397 that leads to caspase-1 sequestration and inactivation. Mice lacking Prdx4 show an increased susceptibility to LPS-induced septic shock. This effect was phenocopied in mice carrying a conditional deletion of Prdx4 in the myeloid lineage (Prdx4-LysMC

SUBMITTER: Dr. Simone Lipinski 

PROVIDER: S-SCDT-EMBOJ-2018-101266 | biostudies-other |

REPOSITORIES: biostudies-other