Article: article from journal or magazin.
Review (review): journal as complete as possible of one specific subject, written based on exhaustive analyses from published work.
Xenotransplantation Model of Psoriasis.
Methods in molecular biology
Publication types: Journal Article
Publication Status: ppublish
Publication Status: ppublish
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.
Animals, Dendritic Cells/immunology, Dendritic Cells/pathology, Dermis/immunology, Dermis/pathology, Disease Models, Animal, Epidermis/immunology, Epidermis/pathology, Flow Cytometry/methods, Humans, Interferon Type I/biosynthesis, Interferon Type I/secretion, Interleukin-23/biosynthesis, Interleukin-23/secretion, Mice, Mice, SCID, Psoriasis/immunology, Psoriasis/pathology, Skin Transplantation/instrumentation, Skin Transplantation/methods, T-Lymphocytes/immunology, T-Lymphocytes/pathology, Transplantation, Heterologous/instrumentation, Transplantation, Heterologous/methods, Preclinical model, Psoriasis, Xenotransplant
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