Prdx4 limits caspase‐1 activation and restricts inflammasome‐mediated signaling by extracellular vesicles
dc.contributor.author | Lipinski, Simone | |
dc.contributor.author | Pfeuffer, Steffen | |
dc.contributor.author | Arnold, Philipp | |
dc.contributor.author | Treitz, Christian | |
dc.contributor.author | Aden, Konrad | |
dc.contributor.author | Ebsen, Henriette | |
dc.contributor.author | Falk‐Paulsen, Maren | |
dc.contributor.author | Gisch, Nicolas | |
dc.contributor.author | Fazio, Antonella | |
dc.contributor.author | Kuiper, Jan | |
dc.contributor.author | Luzius, Anne | |
dc.contributor.author | Billmann‐Born, Susanne | |
dc.contributor.author | Schreiber, Stefan | |
dc.contributor.author | Nuñez, Gabriel | |
dc.contributor.author | Beer, Hans‐Dietmar | |
dc.contributor.author | Strowig, Till | |
dc.contributor.author | Lamkanfi, Mohamed | |
dc.contributor.author | Tholey, Andreas | |
dc.contributor.author | Rosenstiel, Philip | |
dc.date.accessioned | 2019-10-09T08:49:40Z | |
dc.date.available | 2019-10-09T08:49:40Z | |
dc.date.issued | 2019-09-23 | |
dc.identifier.citation | EMBO J. 2019 Sep 23:e101266. doi: 10.15252/embj.2018101266. | en_US |
dc.identifier.issn | 0261-4189 | |
dc.identifier.issn | 1460-2075 | |
dc.identifier.pmid | 31544965 | |
dc.identifier.doi | 10.15252/embj.2018101266 | |
dc.identifier.uri | http://hdl.handle.net/10033/621967 | |
dc.description.abstract | Inflammasomes 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 EVs | en_US |
dc.publisher | EMBO Press | en_US |
dc.rights | Attribution-NonCommercial-ShareAlike 4.0 International | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-sa/4.0/ | * |
dc.subject | General Biochemistry, Genetics and Molecular Biology | en_US |
dc.subject | General Immunology and Microbiology | en_US |
dc.subject | General Neuroscience | en_US |
dc.subject | Molecular Biology | en_US |
dc.title | Prdx4 limits caspase‐1 activation and restricts inflammasome‐mediated signaling by extracellular vesicles | en_US |
dc.type | Article | en_US |
dc.contributor.department | HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. | en_US |
dc.identifier.journal | The EMBO Journal | en_US |
refterms.dateFOA | 2019-10-09T08:49:41Z |