title: Xenotransplantation Model of Psoriasis.
abstract: Psoriasis is a chronic autoimmune skin disease affecting approximately 2 % of the population with a major psychosocial and socioeconomic impact. A causal therapy leading to permanent cure is not available, and current treatments only lead to limited amelioration, and therefore new therapeutic targets need to be identified. Recent works demonstrated a predominant role of TH17 cells in the pathogenesis of psoriasis; yet the underlying molecular mechanisms driving the development of the disease are still largely elusive. Several mouse models of psoriasis including drug-induced models (topical application of imiquimod to the skin) and genetically engineered mice (constitutive activation of epidermal STAT3, epidermal deletion of JunB/c-Jun, and epidermal overexpression of Tie2) have been used to study the pathophysiology of the disease; however such models cannot fully recapitulate all molecular and cellular pathways occurring in human psoriasis. Xenotransplantation of human pre-psoriatic skin onto immunodeficient mice and triggering its conversion into a psoriatic plaque is the best model to dissect the mechanisms occurring during the development of human psoriasis. One model is based on the transplantation of human pre-psoriatic skin onto SCID mice followed by the transfer of activated autologous T cells. The ex vivo activation of T cells required to induce the psoriatic conversion of the graft limits the study of early events in the pathogenesis of psoriasis. Another model is based on transplantation of human pre-psoriatic skin onto AGR129 mice. In this model, the skin grafting is sufficient to activate human cells contained in the graft and trigger the conversion of the graft into a psoriatic skin, without the need of transferring activated T cells. Here we review the methodological aspects of this model and illustrate how this model can be used to dissect early events of psoriasis pathogenesis.
authors.affiliation: Department of Dermatology, University Hospital CHUV, Avenue de Beaumont 29, 1011, Lausanne, Switzerland.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Di Domizio
authors.affiliation: Department of Dermatology, University Hospital CHUV, Avenue de Beaumont 29, 1011, Lausanne, Switzerland.
authors.forename: Curdin
authors.initials: C
authors.lastname: Conrad
authors.affiliation: Department of Dermatology, University Hospital CHUV, Avenue de Beaumont 29, 1011, Lausanne, Switzerland. Michel.gilliet@chuv.ch.
authors.forename: Michel
authors.initials: M
authors.lastname: Gilliet
mesh_terms: D000818:Animals; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D020405:Dermis / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D004817:Epidermis / Q000276:immunology / Q000473:pathology; D005434:Flow Cytometry / Q000379:methods*; D006801:Humans; D007370:Interferon Type I / Q000096:biosynthesis / Q000378:metabolism; D053759:Interleukin-23 / Q000096:biosynthesis / Q000378:metabolism; D051379:Mice; D016513:Mice, SCID; D011565:Psoriasis / Q000276:immunology* / Q000473:pathology; D016038:Skin Transplantation / Q000295:instrumentation / Q000379:methods*; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D014183:Transplantation, Heterologous / Q000295:instrumentation / Q000379:methods*
chemical_list: D007370:Interferon Type I; D053759:Interleukin-23
keywords: Preclinical model; Psoriasis; Xenotransplant