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  1. Article ; Online: 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

    2023  Volume 18, Issue 1, Page(s) e0278390

    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 ... ...

    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.
    MeSH term(s) Humans ; Mice ; Animals ; Transplantation, Heterologous ; Interleukin-2 ; T-Lymphocytes/pathology ; Skin/pathology ; Psoriasis/pathology
    Chemical Substances Interleukin-2
    Language English
    Publishing date 2023-01-17
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0278390
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Imiquimod induces skin inflammation in humanized BRGSF mice with limited human immune cell activity.

    Christensen, Pernille Kristine Fisker / Hansen, Axel Kornerup / Skov, Søren / Martel, Britta Cathrina / Larsen, Jesper / Høyer-Hansen, Maria Helena / Koch, Janne

    PloS one

    2023  Volume 18, Issue 2, Page(s) e0281005

    Abstract: Human immune system (HIS) mouse models can be valuable when cross-reactivity of drug candidates to mouse systems is missing. However, no HIS mouse models of psoriasis have been established. In this study, it was investigated if imiquimod (IMQ) induced ... ...

    Abstract Human immune system (HIS) mouse models can be valuable when cross-reactivity of drug candidates to mouse systems is missing. However, no HIS mouse models of psoriasis have been established. In this study, it was investigated if imiquimod (IMQ) induced psoriasis-like skin inflammation was driven by human immune cells in human FMS-related tyrosine kinase 3 ligand (hFlt3L) boosted (BRGSF-HIS mice). BRGSF-HIS mice were boosted with hFlt3L prior to two or three topical applications of IMQ. Despite clinical skin inflammation, increased epidermal thickness and influx of human immune cells, a human derived response was not pronounced in IMQ treated mice. However, the number of murine neutrophils and murine cytokines and chemokines were increased in the skin and systemically after IMQ application. In conclusion, IMQ did induce skin inflammation in hFlt3L boosted BRGSF-HIS mice, although, a limited human immune response suggest that the main driving cellular mechanisms were of murine origin.
    MeSH term(s) Humans ; Mice ; Animals ; Imiquimod/adverse effects ; Dermatitis ; Skin ; Psoriasis/drug therapy ; Inflammation/chemically induced ; Disease Models, Animal
    Chemical Substances Imiquimod (P1QW714R7M)
    Language English
    Publishing date 2023-02-17
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0281005
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

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