Reducing Flightless I expression decreases severity of psoriasis in an imiquimod-induced murine model of psoriasiform dermatitis
Date
2017
Authors
Chong, H.
Yang, G.
Sidhu, S.
Ibbetson, J.
Kopecki, Z.
Cowin, A.
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Journal article
Citation
British Journal of Dermatology, 2017; 176(3):705-712
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H.T. Chong, G.N. Yang, S. Sidhu, J. Ibbetson, Z. Kopecki and A.J. Cowin
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Abstract
Psoriasis 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.
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© 2016 British Association of Dermatologists