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dc.contributor.authorLipinski, Simone
dc.contributor.authorPfeuffer, Steffen
dc.contributor.authorArnold, Philipp
dc.contributor.authorTreitz, Christian
dc.contributor.authorAden, Konrad
dc.contributor.authorEbsen, Henriette
dc.contributor.authorFalk‐Paulsen, Maren
dc.contributor.authorGisch, Nicolas
dc.contributor.authorFazio, Antonella
dc.contributor.authorKuiper, Jan
dc.contributor.authorLuzius, Anne
dc.contributor.authorBillmann‐Born, Susanne
dc.contributor.authorSchreiber, Stefan
dc.contributor.authorNuñez, Gabriel
dc.contributor.authorBeer, Hans‐Dietmar
dc.contributor.authorStrowig, Till
dc.contributor.authorLamkanfi, Mohamed
dc.contributor.authorTholey, Andreas
dc.contributor.authorRosenstiel, Philip
dc.identifier.citationEMBO J. 2019 Sep 23:e101266. doi: 10.15252/embj.2018101266.en_US
dc.description.abstractInflammasomes are cytosolic protein complexes, which orchestrate the maturation of active IL-1β 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-1β 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-ΔLysMCre). Strikingly, we demonstrate that Prdx4 co-localizes with inflammasome components in extracellular vesicles (EVs) from inflammasome-activated macrophages. Purified EVs are able to transmit a robust IL-1β-dependent inflammatory response in vitro and also in recipient mice in vivo. Loss of Prdx4 boosts the pro-inflammatory potential of EVs. These findings identify Prdx4 as a critical regulator of inflammasome activity and provide new insights into remote cell-to-cell communication function of inflammasomes via macrophage-derived EVsen_US
dc.publisherEMBO Pressen_US
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International*
dc.subjectGeneral Biochemistry, Genetics and Molecular Biologyen_US
dc.subjectGeneral Immunology and Microbiologyen_US
dc.subjectGeneral Neuroscienceen_US
dc.subjectMolecular Biologyen_US
dc.titlePrdx4 limits caspase‐1 activation and restricts inflammasome‐mediated signaling by extracellular vesiclesen_US
dc.contributor.departmentHZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.en_US
dc.identifier.journalThe EMBO Journalen_US

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