Please use this identifier to cite or link to this item: http://doi.org/10.25358/openscience-799
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dc.contributor.authorWeng, Shih-Yen-
dc.contributor.authorWang, Xiaoyu-
dc.contributor.authorVijayan, Santosh-
dc.contributor.authorTang, Yilang-
dc.contributor.authorKim, Yong Ook-
dc.contributor.authorPadberg, Kornelius-
dc.contributor.authorRegen, Tommy-
dc.contributor.authorMolokanova, Olena-
dc.contributor.authorChen, Tao-
dc.contributor.authorBopp, Tobias-
dc.contributor.authorSchild, Hansjörg-
dc.contributor.authorBrombacher, Frank-
dc.contributor.authorCrosby, Jeff R.-
dc.contributor.authorMcCaleb, Michael L.-
dc.contributor.authorWaisman, Ari-
dc.contributor.authorBockamp, Ernesto-
dc.contributor.authorSchuppan, Detlef-
dc.date.accessioned2018-08-02T09:29:44Z-
dc.date.available2018-08-02T11:29:44Z-
dc.date.issued2018-
dc.identifier.urihttps://openscience.ub.uni-mainz.de/handle/20.500.12030/801-
dc.description.abstractChronic hepatitis leads to liver fibrosis and cirrhosis. Cirrhosis is a major cause ofworldwide morbidity and mortality. Macrophages play a key role in fibrosis progression and reversal. However, the signals that determine fibrogenic vs fibrolytic macrophage function remain ill defined. We studied the role of interleukin-4 receptor α (IL-4Rα), a potential central switch of macrophage polarization, in liver fibrosis progression and reversal. We demonstrate that inflammatory monocyte infiltration and liver fibrogenesis were suppressed in general IL-4Rα−/− aswell as in macrophage-specific IL-4Rα−/− (IL-4RαΔLysM) mice. However,with deletion of IL-4RαΔLysM spontaneous fibrosis reversal was retarded. Results were replicated by pharmacological intervention using IL-4Rα-specific antisense oligonucleotides. Retarded resolution was linked to the loss of M2-type resident macrophages, which secreted MMP-12 through IL-4 and IL-13-mediated phospho-STAT6 activation. We conclude that IL-4Rα signaling regulates macrophage functional polarization in a context-dependent manner. Pharmacological targeting of macrophage polarization therefore requires disease stage-specific treatment strategies. Research in Context: Alternative (M2-type) macrophage activation through IL-4Rα promotes liver Inflammation and fibrosis progression but speeds up fibrosis reversal. This demonstrates context dependent, opposing roles of M2-type macrophages. During reversal IL-4Rα induces fibrolytic MMPs, especially MMP-12, through STAT6. Liver-specific antisense oligonucleotides efficiently block IL-4Rα expression and attenuate fibrosis progression.en_GB
dc.description.sponsorshipDFG, Open Access-Publizieren Universität Mainz / Universitätsmedizin-
dc.language.isoeng-
dc.rightsCC BY-NC-NDde_DE
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/-
dc.subject.ddc610 Medizinde_DE
dc.subject.ddc610 Medical sciencesen_GB
dc.titleIL-4 receptor alpha signaling through macrophages differentially regulates liver fibrosis progression and reversalen_GB
dc.typeZeitschriftenaufsatzde_DE
dc.identifier.urnurn:nbn:de:hebis:77-publ-584084-
dc.identifier.doihttp://doi.org/10.25358/openscience-799-
jgu.type.dinitypearticle-
jgu.type.versionPublished versionen_GB
jgu.type.resourceText-
jgu.organisation.departmentFB 04 Medizin-
jgu.organisation.number2700-
jgu.organisation.nameJohannes Gutenberg-Universität Mainz-
jgu.rights.accessrightsopenAccess-
jgu.journal.titleEBioMedicine-
jgu.journal.volume29-
jgu.pages.start92-
jgu.pages.end103-
jgu.publisher.year2018-
jgu.publisher.nameElsevier-
jgu.publisher.placeAmsterdam-
jgu.publisher.urihttp://dx.doi.org/10.1016/j.ebiom.2018.01.028-
jgu.publisher.issn2352-3964-
jgu.organisation.placeMainz-
jgu.subject.ddccode610-
opus.date.accessioned2018-08-02T09:29:44Z-
opus.date.modified2018-09-03T07:44:18Z-
opus.date.available2018-08-02T11:29:44-
opus.subject.dfgcode00-000-
opus.organisation.stringFB 04: Medizin: Institut für Immunologiede_DE
opus.organisation.stringFB 04: Medizin: Institut für Molekulare Medizinde_DE
opus.organisation.stringFB 04: Medizin: Institut für Translationale Immunologie (TIM)de_DE
opus.organisation.stringFB 04: Medizin: Forschungszentrum für Immuntherapie (FZI)de_DE
opus.identifier.opusid58408-
opus.institute.number0412-
opus.institute.number0458-
opus.institute.number0475-
opus.institute.number0476-
opus.metadataonlyfalse-
opus.type.contenttypeKeinede_DE
opus.type.contenttypeNoneen_GB
opus.affiliatedBopp, Tobias-
opus.affiliatedSchild, Hansjörg-
opus.affiliatedWaisman, Ari-
opus.affiliatedSchuppan, Detlef-
jgu.publisher.doi10.1016/j.ebiom.2018.01.028
jgu.organisation.rorhttps://ror.org/023b0x485
Appears in collections:JGU-Publikationen

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