LEO Pharma A/S, Ballerup, Denmark.
Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg C, Denmark.
PLoS One. 2023 Jan 17;18(1):e0278390. doi: 10.1371/journal.pone.0278390. eCollection 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.
将银屑病皮肤移植到免疫缺陷小鼠中已被广泛用于获得新药候选物的原理验证。然而，移植物中缺乏人类 T 细胞活性限制了该模型的使用。在这里，我们表明，将银屑病患者的皮损皮肤移植到人类 IL-2 NOG 小鼠中，与 C.B-17 scid 和 NOG 小鼠相比，移植物、腋窝淋巴结和人 IL-2 NOG 小鼠的血液中人类 CD3+细胞数量增加。此外，移植物裂解物和人 IL-2 NOG 小鼠血清中的疾病相关人类细胞因子水平更高。然而，表皮缺失，且针对 IL-12 和 IL-23 的人抗 P40 抗体乌司奴单抗没有显示出疗效。因此，尽管 T 细胞活性持续存在，但该模型需要进一步研究和验证，以捕获银屑病的更多方面。
