Review paper: preclinical models of psoriasis.
Psoriasis is the most common autoimmune disease in man and is characterized by focal to coalescing raised cutaneous plaques with consistent scaling and variable erythema. The specific pathogenesis of psoriasis is not completely understood, but the underlying mechanisms involve a complex interplay between epidermal keratinocytes, T lymphocytes as well as other leukocytes (including dendritic cells and other antigen presenting cells [APCs]), and vascular endothelium. Mirroring the complexity of mechanisms that underlie psoriasis, there are a relatively large number of models of psoriasis. Each model is based on a slightly different pathogenic mechanism, and each has its similarities to psoriasis as well as its limitations. In general, psoriasis models can be very broadly divided on the basis of the pathogenic mechanisms that interplay to cause psoriasis, with the addition of several relatively poorly defined spontaneous murine mutant models. Other than the spontaneous mutant models, murine models of psoriasis can be divided into those that are genetically engineered (transgenic and knockout-with manipulation of either the epidermis, leukocytes, or the endothelium), and those that are induced (either by immune transfer or by xenotransplantation of skin from psoriatic patients). In addition to the murine models, in vitro human epidermal models have recently become more widely utilized. While no one single model of psoriasis is ideal, many have proven to be extremely valuable in investigating and better understanding the molecular mechanisms that underlie the complex interplay between epidermal keratinocytes, the innate and adaptive immune system, and the vascular endothelium in psoriasis.
Danilenko
D M
DM
Genentech, Inc., Department of Pathology, One DNA Way, MS 72B, South San Francisco, CA 94080, USA. danilenko.dimitry@gene.com
D000818:Animals; D030801:Animals, Genetically Modified; D004195:Disease Models, Animal; D015603:Keratinocytes / Q000276:immunology / Q000473:pathology; D051379:Mice; D011565:Psoriasis / Q000276:immunology / Q000473:pathology; D051381:Rats; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology