Animal models of psoriasis

Abstract

Research into the pathogenesis of psoriasis has been severely hampered by the lack of a naturally occurring disorder in laboratory animals that mimics the complex phenotype and pathogenesis of the human disease. A large variety of spontaneous mutations, genetically engineered rodents, immunological reconstitution approaches, and xenotransplantation models have been used to study specific aspects of the pathophysiology of psoriasis, however. Several manipulations of resident cutaneous cell types or immigrating immunocytes appear to result in remarkably similar hyperproliferative inflammatory phenotypes in mice, thus suggesting that interfering with cutaneous homeostasis in general may ultimately result in a rather uniform reaction pattern that mirrors some features of psoriasis. Fully animal models of psoriasis have nonetheless not only shed light on the biological functions of given inflammatory mediators or other molecules but also tremendously contributed to the discussion on central pathogenic questions, such as the roles of innate and adaptive immune mechanisms, keratinocytes, and endothelial cells in psoriasis. Psoriasis research has also been greatly nourished by xenotransplantation of diseased or unaffected human skin onto immunocompromised recipients, an approach that has in many variations been used to study the role of T lymphocytes and other cells and that has been used for preclinical therapeutic studies. General approaches to generate animal models of psoriasis, features of some specific models, their value for psoriasis research, and their use for drug development are discussed in this article.