Sustaining the T-cell activity in xenografted psoriasis skin

维持异种移植银屑病皮肤中的 T 细胞活性

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作者:Pernille Kristine Fisker Christensen, Axel Kornerup Hansen, Søren Skov, Kåre Engkilde, Jesper Larsen, Maria Helena Høyer-Hansen, Janne Koch

Abstract

Xenografting of psoriasis skin onto immune deficient mice has been widely used to obtain proof-of-principle of new drug candidates. However, the lack of human T-cell activity in the grafts limits the use of the model. Here, we show that xenografting of lesional skin from psoriasis patients onto human IL-2 NOG mice results in increased numbers of human CD3+ cells in the grafts, axillary lymph nodes and blood from human IL-2 NOG mice compared to C.B-17 scid and NOG mice. In addition, disease relevant human cytokine levels were higher in graft lysates and serum from human IL-2 NOG mice. However, the epidermis was lacking and no efficacy of ustekinumab, a human anti-P40 antibody targeting both IL-12 and IL-23, was shown. Thus, despite the sustained T-cell activity, the model needs further investigations and validation to capture more aspects of psoriasis.

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