Psoriasis: what we have learned from mouse models

• Published in: Nature reviews. Rheumatology Vol. 6; no. 12; pp. 704 - 714
• Main Authors: Wagner, Erwin F, Schonthaler, Helia B, Guinea-Viniegra, Juan, Tschachler, Erwin
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.12.2010; Nature Publishing Group
• Subjects: 631/154/555; 631/1647/334/1874/345; 631/80/304; 692/699/249/2510/1758; Animals; Arthritis; Care and treatment; Cell Differentiation - physiology; Diagnosis; Disease Models, Animal; Health aspects; Histopathology; Humans; Keratinocytes - pathology; Lymphocytes; Medicine; Medicine & Public Health; Mice; Mice, Knockout; Mice, Transgenic; Neutrophils; Pathogenesis; Patients; Psoriasis; Psoriasis - drug therapy; Psoriasis - genetics; Psoriasis - physiopathology; review-article; Rheumatology; Risk factors; Signal Transduction - physiology; Skin diseases; Transplantation, Heterologous; Xenotransplantation; Austria
• ISSN: 1759-4790; 1759-4804
• DOI: 10.1038/nrrheum.2010.157

Psoriasis is only observed in humans; however, characteristics of the disease, such as prominent epidermal hyperplasia and a distinct inflammatory infiltrate, have been studied in mouse models of psoriasis. In this Review, the authors highlight the mouse models that have contributed to the discovery of novel disease-relevant pathways. Psoriasis is a common inflammatory skin disease of unknown etiology, for which there is no cure. This heterogeneous, cutaneous, inflammatory disorder is clinically characterized by prominent epidermal hyperplasia and a distinct inflammatory infiltrate. Crosstalk between immunocytes and keratinocytes, which results in the production of cytokines, chemokines and growth factors, is thought to mediate the disease. Given that psoriasis is only observed in humans, numerous genetic approaches to model the disease in mice have been undertaken. In this Review, we describe and critically assess the mouse models and transplantation experiments that have contributed to the discovery of novel disease-relevant pathways in psoriasis. Research performed using improved mouse models, combined with studies employing human cells, xenografts and patient material, will be key to our understanding of why such distinctive patterns of inflammation develop in patients with psoriasis. Indeed, a combination of genetic and immunological investigations will be necessary to develop both improved drugs for the treatment of psoriasis and novel curative strategies. Key Points Psoriasis is a common inflammatory skin disease that is genetically heterogeneous and for which there is currently no cure Mouse models do not reproduce all aspects of psoriasis, but are nevertheless important tools to dissect the molecular and cellular events underlying the pathophysiology of the disease Increased understanding of the complexity of psoriasis could be achieved by the development of improved mouse models and xenotransplantation studies involving cell transfer and tissue grafts Novel strategies to treat psoriasis are likely to derive from the identification of new targets and the use of mouse models for drug testing