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  2. Johannes Gutenberg-Universität Mainz
  3. DFG-491381577-H
Please use this identifier to cite or link to this item: http://doi.org/10.25358/openscience-8546
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dc.contributor.authorFleischer, Maria Isabel-
dc.contributor.authorRöhrig, Nadine-
dc.contributor.authorRaker, Verena K.-
dc.contributor.authorSpringer, Juliane-
dc.contributor.authorBecker, Detlef-
dc.contributor.authorRitz, Sandra-
dc.contributor.authorBros, Matthias-
dc.contributor.authorStege, Henner-
dc.contributor.authorHaist, Maximilian-
dc.contributor.authorGrabbe, Stephan-
dc.contributor.authorHaub, Jessica-
dc.contributor.authorBecker, Christian-
dc.contributor.authorReyda, Sabine-
dc.contributor.authorDisse, Jennifer-
dc.contributor.authorSchmidt, Talkea-
dc.contributor.authorMahnke, Karsten-
dc.contributor.authorWeiler, Hartmut-
dc.contributor.authorRuf, Wolfram-
dc.contributor.authorSteinbrik, Kerstin-
dc.date.accessioned2023-01-10T11:42:30Z-
dc.date.available2023-01-10T11:42:30Z-
dc.date.issued2022-
dc.identifier.urihttps://openscience.ub.uni-mainz.de/handle/20.500.12030/8562-
dc.description.abstractBackground: Protease-activated receptor 2 (PAR2) signaling controls skin barrier function and inflammation, but the roles of immune cells and PAR2-activating pro teases in cutaneous diseases are poorly understood. Objective: To dissect PAR2 signaling contributions to skin inflammation with new ge netic and pharmacological tools. Methods/Results: We found markedly increased numbers of PAR2+ infiltrating my eloid cells in skin lesions of allergic contact dermatitis (ACD) patients and in the skin of contact hypersensitivity (CHS) in mice, a murine ACD model for T cell–mediated allergic skin inflammation. Cell type–specific deletion of PAR2 in myeloid immune cells as well as mutation-induced complete PAR2 cleavage insensitivity significantly re duced skin inflammation and hapten-specific Tc1/Th1 cell response. Pharmacological approaches identified individual proteases involved in PAR2 cleavage and demon strated a pivotal role of tissue factor (TF) and coagulation factor Xa (FXa) as upstream activators of PAR2 in both the induction and effector phase of CHS. PAR2 mutant mouse strains with differential cleavage sensitivity for FXa versus skin epithelial cell–expressed proteases furthermore uncovered a time-dependent regulation of CHS development with an important function of FXa-induced PAR2 activation during the late phase of skin inflammation. Conclusions: Myeloid cells and the TF–FXa–PAR2 axis are key mediators and poten tial therapeutic targets in inflammatory skin diseasesen_GB
dc.description.sponsorshipGefördert durch die Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 491381577de
dc.language.isoengde
dc.rightsCC BY-NC-ND*
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subject.ddc610 Medizinde_DE
dc.subject.ddc610 Medical sciencesen_GB
dc.titleProtease- and cell type–specific activation of protease-activated receptor 2 in cutaneous inflammationen_GB
dc.typeZeitschriftenaufsatzde
dc.identifier.doihttp://doi.org/10.25358/openscience-8546-
jgu.type.dinitypearticleen_GB
jgu.type.versionPublished versionde
jgu.type.resourceTextde
jgu.organisation.departmentFB 04 Medizinde
jgu.organisation.number2700-
jgu.organisation.nameJohannes Gutenberg-Universität Mainz-
jgu.rights.accessrightsopenAccess-
jgu.journal.titleJournal of thrombosis and haemostasisde
jgu.journal.volume20de
jgu.journal.issue12de
jgu.pages.start2823de
jgu.pages.end2836de
jgu.publisher.year2022-
jgu.publisher.nameWiley-Blackwellde
jgu.publisher.placeOxfordde
jgu.publisher.issn1538-7836de
jgu.organisation.placeMainz-
jgu.subject.ddccode610de
jgu.publisher.doi10.1111/jth.15894de
jgu.organisation.rorhttps://ror.org/023b0x485-
jgu.subject.dfgLebenswissenschaftende
Appears in collections:DFG-491381577-H

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