Sustaining the T-cell activity in xenografted psoriasis skin
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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.
I: PLoS ONE, Bind 18, e0278390, 2023.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Sustaining the T-cell activity in xenografted psoriasis skin
AU - Christensen, Pernille Kristine Fisker
AU - Hansen, Axel Kornerup
AU - Skov, Søren
AU - Engkilde, Kåre
AU - Larsen, Jesper
AU - Høyer-Hansen, Maria Helena
AU - Koch, Janne
N1 - Publisher Copyright: © 2023 Christensen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
U2 - 10.1371/journal.pone.0278390
DO - 10.1371/journal.pone.0278390
M3 - Journal article
C2 - 36649237
AN - SCOPUS:85146484704
VL - 18
JO - PLoS ONE
JF - PLoS ONE
SN - 1932-6203
M1 - e0278390
ER -
ID: 334260850