Sustaining the T-cell activity in xenografted psoriasis skin.
Pernille Kristine Fisker ChristensenAxel Kornerup HansenSøren SkovKåre EngkildeJesper LarsenMaria Helena Høyer-HansenJanne KochPublished in: PloS one (2023)
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.
Keyphrases
- endothelial cells
- induced pluripotent stem cells
- lymph node
- pluripotent stem cells
- end stage renal disease
- emergency department
- chronic kidney disease
- cell proliferation
- cell death
- high fat diet induced
- insulin resistance
- skeletal muscle
- metabolic syndrome
- peritoneal dialysis
- neoadjuvant chemotherapy
- induced apoptosis
- drug delivery
- sentinel lymph node
- endoplasmic reticulum stress
- atopic dermatitis
- cell cycle arrest
- electronic health record
- hidradenitis suppurativa