Animal models of psoriasis: a critical appraisal

Abstract

Abstract:  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.