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dc.contributor.authorBieber, Katja
dc.contributor.authorBezdek, Siegfried
dc.contributor.authorGupta, Yask
dc.contributor.authorVorobyev, Artem
dc.contributor.authorSezin, Tanya
dc.contributor.authorGross, Natalie
dc.contributor.authorPrüssmann, Jasper
dc.contributor.authorSayegh, Jean-Paul
dc.contributor.authorBecker, Mareike
dc.contributor.authorMousavi, Sadegh
dc.contributor.authorHdnah, Ashref
dc.contributor.authorKünzel, Sven
dc.contributor.authorIbrahim, Saleh M
dc.contributor.authorLudwig, Ralf J
dc.contributor.authorGullberg, Elon Donald
dc.contributor.authorSadik, Christian D
dc.date.accessioned2024-08-23T10:34:58Z
dc.date.available2024-08-23T10:34:58Z
dc.date.created2023-10-10T13:50:33Z
dc.date.issued2023
dc.identifier.issn0022-3417
dc.identifier.urihttps://hdl.handle.net/11250/3147817
dc.description.abstractPsoriasis is a chronic inflammatory skin condition. Repeated epicutaneous application of Aldara® (imiquimod) cream results in psoriasiform dermatitis in mice. The Aldara®-induced psoriasiform dermatitis (AIPD) mouse model has been used to examine the pathogenesis of psoriasis. Here, we used a forward genetics approach in which we compared AIPD that developed in 13 different inbred mouse strains to identify genes and pathways that modulated disease severity. Among our primary results, we found that the severity of AIPD differed substantially between different strains of inbred mice and that these variations were associated with polymorphisms in Itga11. The Itga11 gene encodes the integrin α11 subunit that heterodimerizes with the integrin β1 subunit to form integrin α11β1. Less information is available about the function of ITGA11 in skin inflammation; however, a role in the regulation of cutaneous wound healing, specifically the development of dermal fibrosis, has been described. Experiments performed with Itga11 gene-deleted (Itga11−/−) mice revealed that the integrin α11 subunit contributes substantially to the clinical phenotype as well as the histopathological and molecular findings associated with skin inflammation characteristic of AIPD. Although the skin transcriptomes of Itga11−/− and WT mice do not differ from one another under physiological conditions, distinct transcriptomes emerge in these strains in response to the induction of AIPD. Most of the differentially expressed genes contributed to extracellular matrix organization, immune system, and metabolism of lipids pathways. Consistent with these findings, we detected a reduced number of fibroblasts and inflammatory cells, including macrophages, T cells, and tissue-resident memory T cells in skin samples from Itga11−/− mice in response to AIPD induction. Collectively, our results reveal that Itga11 plays a critical role in promoting skin inflammation in AIPD and thus might be targeted for the development of novel therapeutics for psoriasiform skin conditions.en_US
dc.language.isoengen_US
dc.publisherWileyen_US
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internasjonal*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/deed.no*
dc.titleForward genetics and functional analysis highlight Itga11 as a modulator of murine psoriasiform dermatitisen_US
dc.typeJournal articleen_US
dc.typePeer revieweden_US
dc.description.versionpublishedVersionen_US
dc.rights.holderCopyright 2023 The Author(s)en_US
cristin.ispublishedtrue
cristin.fulltextoriginal
cristin.qualitycode2
dc.identifier.doi10.1002/path.6162
dc.identifier.cristin2183388
dc.source.journalJournal of Pathologyen_US
dc.source.pagenumber184-197en_US
dc.relation.projectKreftforeningen: 223052en_US
dc.relation.projectNorges forskningsråd: 223250en_US
dc.identifier.citationJournal of Pathology. 2023, 261 (2), 184-197.en_US
dc.source.volume261en_US
dc.source.issue2en_US


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Attribution-NonCommercial-NoDerivatives 4.0 Internasjonal
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