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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2023
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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. |
format | Online Article Text |
id | pubmed-9844869 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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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