Reducing Flightless I expression decreases severity of psoriasis in an imiquimod-induced murine model of psoriasiform dermatitis

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dc.contributor.authorChong, H.
dc.contributor.authorYang, G.
dc.contributor.authorSidhu, S.
dc.contributor.authorIbbetson, J.
dc.contributor.authorKopecki, Z.
dc.contributor.authorCowin, A.
dc.date.issued2017
dc.description.abstractPsoriasis is a common chronic skin condition characterized by excessive inflammation and aberrant epidermal proliferation. Flightless I (Flii) is an actin-remodelling protein that regulates these processes, suggesting a possible role in psoriasis.We sought to determine whether a benefit in psoriasiform dermatitis might occur after modulating Flii gene expression or reducing its levels using neutralizing antibodies.Biopsies of psoriatic skin lesions from patients were assessed for Flii levels. Psoriasis-like lesions were induced in Flii heterozygous (Flii+/- ), wild-type (Flii+/+ ) and Flii transgenic (FliiTg/Tg ) mice using topical application of imiquimod. Additionally, psoriasis-induced wild-type mice were treated with topical application of Flii neutralizing antibodies and erythema, inflammation and histology were assessed.Flii was elevated in psoriatic lesions from patients with psoriasis compared with normal human skin. Reducing Flii decreased erythema, inflammatory cell infiltrate, proinflammatory cytokines and the thickness of the epidermis. Topical application of Flii neutralizing antibodies to wild-type mice treated with imiquimod resulted in significantly reduced psoriasiform dermatitis.Flii is a novel target involved in psoriasiform dermatitis and reducing cutaneous Flii could potentially be a new approach for treating patients with psoriasis.
dc.description.statementofresponsibilityH.T. Chong, G.N. Yang, S. Sidhu, J. Ibbetson, Z. Kopecki and A.J. Cowin
dc.identifier.citationBritish Journal of Dermatology, 2017; 176(3):705-712
dc.identifier.doi10.1111/bjd.14842
dc.identifier.issn0007-0963
dc.identifier.issn1365-2133
dc.identifier.orcidKopecki, Z. [0000-0002-8072-4222]
dc.identifier.orcidCowin, A. [0000-0003-2885-2080]
dc.identifier.urihttp://hdl.handle.net/2440/105716
dc.language.isoen
dc.publisherWiley
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1002009
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1036509
dc.rights© 2016 British Association of Dermatologists
dc.source.urihttps://doi.org/10.1111/bjd.14842
dc.subjectAnimals
dc.subjectMice, Inbred BALB C
dc.subjectHumans
dc.subjectDermatitis
dc.subjectDrug Eruptions
dc.subjectPsoriasis
dc.subjectDisease Models, Animal
dc.subjectAminoquinolines
dc.subjectMicrofilament Proteins
dc.subjectCarrier Proteins
dc.subjectCytoskeletal Proteins
dc.subjectTrans-Activators
dc.subjectRNA, Messenger
dc.subjectAntibodies, Monoclonal
dc.subjectIrritants
dc.subjectAdministration, Cutaneous
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectMale
dc.subjectToll-Like Receptor 4
dc.subjectAntibodies, Neutralizing
dc.subjectImiquimod
dc.titleReducing Flightless I expression decreases severity of psoriasis in an imiquimod-induced murine model of psoriasiform dermatitis
dc.typeJournal article
pubs.publication-statusPublished

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