Schön Michael P
Department of Dermatology, University of Göttingen, Göttingen, Germany.
Exp Dermatol. 2008 Aug;17(8):703-12. doi: 10.1111/j.1600-0625.2008.00751.x. Epub 2008 Jun 28.
Although there is no naturally occurring disorder in laboratory animals that mimics the complex phenotype of psoriasis, a large number of spontaneous or genetically engineered mutations in rodents, immunological reconstitution approaches or xenotransplantation models have shed light on specific aspects implicated in the pathophysiology and therapy of psoriasis. Animal models have helped to elucidate functions of inflammatory mediators or to unravel the contribution of innate or adaptive immune mechanisms, keratinocytes or endothelial cells to chronic hyperproliferative inflammatory skin disorders. However, given that several distinct manipulations of molecular pathways, resident cutaneous cell types or immigrating immunocytes result in remarkably similar phenotypes in experimental animals, it appears that interfering with cutaneous homeostasis in general may ultimately initiate a rather uniform reaction pattern that mirrors some features of psoriasis. This limitation of animal models generated without the use of human material may, at least in part, be overcome by xenotransplantation of human skin onto immunocompromised animals. The latter approach has been employed in preclinical investigations to study the role of immune cells and/or to predict the efficacy of some therapeutic compounds. This brief review delineates approaches to generate animal models of psoriasis and discusses their strengths and limitations for psoriasis research.
尽管实验动物中没有自然发生的疾病能模拟银屑病的复杂表型,但啮齿动物中的大量自发或基因工程突变、免疫重建方法或异种移植模型,已为银屑病病理生理学和治疗中涉及的特定方面提供了线索。动物模型有助于阐明炎症介质的功能,或揭示先天性或适应性免疫机制、角质形成细胞或内皮细胞对慢性过度增殖性炎症性皮肤病的作用。然而,鉴于对分子途径、常驻皮肤细胞类型或迁移免疫细胞的几种不同操作在实验动物中会产生非常相似的表型,似乎一般而言干扰皮肤稳态最终可能引发一种相当统一的反应模式,该模式反映了银屑病的一些特征。通过将人类皮肤异种移植到免疫受损动物身上,至少部分地可以克服不使用人类材料产生的动物模型的这一局限性。后一种方法已用于临床前研究,以研究免疫细胞的作用和/或预测某些治疗化合物的疗效。这篇简短的综述阐述了生成银屑病动物模型的方法,并讨论了它们在银屑病研究中的优势和局限性。