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Sustaining the T-cell activity in xenografted psoriasis skin

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 huma...

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Autores principales: Christensen, Pernille Kristine Fisker, Hansen, Axel Kornerup, Skov, Søren, Engkilde, Kåre, Larsen, Jesper, Høyer-Hansen, Maria Helena, Koch, Janne
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9844869/
https://www.ncbi.nlm.nih.gov/pubmed/36649237
http://dx.doi.org/10.1371/journal.pone.0278390
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author Christensen, Pernille Kristine Fisker
Hansen, Axel Kornerup
Skov, Søren
Engkilde, Kåre
Larsen, Jesper
Høyer-Hansen, Maria Helena
Koch, Janne
author_facet Christensen, Pernille Kristine Fisker
Hansen, Axel Kornerup
Skov, Søren
Engkilde, Kåre
Larsen, Jesper
Høyer-Hansen, Maria Helena
Koch, Janne
author_sort Christensen, Pernille Kristine Fisker
collection PubMed
description 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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spelling pubmed-98448692023-01-18 Sustaining the T-cell activity in xenografted psoriasis skin Christensen, Pernille Kristine Fisker Hansen, Axel Kornerup Skov, Søren Engkilde, Kåre Larsen, Jesper Høyer-Hansen, Maria Helena Koch, Janne PLoS One Research Article 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. Public Library of Science 2023-01-17 /pmc/articles/PMC9844869/ /pubmed/36649237 http://dx.doi.org/10.1371/journal.pone.0278390 Text en © 2023 Christensen et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Christensen, Pernille Kristine Fisker
Hansen, Axel Kornerup
Skov, Søren
Engkilde, Kåre
Larsen, Jesper
Høyer-Hansen, Maria Helena
Koch, Janne
Sustaining the T-cell activity in xenografted psoriasis skin
title Sustaining the T-cell activity in xenografted psoriasis skin
title_full Sustaining the T-cell activity in xenografted psoriasis skin
title_fullStr Sustaining the T-cell activity in xenografted psoriasis skin
title_full_unstemmed Sustaining the T-cell activity in xenografted psoriasis skin
title_short Sustaining the T-cell activity in xenografted psoriasis skin
title_sort sustaining the t-cell activity in xenografted psoriasis skin
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9844869/
https://www.ncbi.nlm.nih.gov/pubmed/36649237
http://dx.doi.org/10.1371/journal.pone.0278390
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