Development of a Bioengineered Skin-Humanized Mouse Model for Psoriasis Dissecting Epidermal-Lymphocyte Interacting Pathways

Over the past few years whole skin xenotransplantation models that mimic different aspects of psoriasis have become available However these models are strongly constrained by the lack of skin donor avail ability and homogeneity We present in this study a bioengineering based skin humanized mouse model for psoriasis either in an autologous version using samples derived from psoriatic patients or more importantly in an allogeneic context starting from skin biopsies and blood samples from unrelated healthy donors After engraftment the regenerated human skin presents the typical architecture of normal human skin but in both cases immunological reconstitution through intradermal injection m the regenerated skin using in vitro-differentiated T1 subpopulations as well as recombinant IL-17 and IL 22 Th17 cytokines together with removal of the stratum corneum barrier by a mild abrasive treatment leads to the rapid con version of the skin into a bona fide psoriatic phenotype Major hallmarks of psoriasis were confirmed by the evaluation of specific epidermal differentiation and proliferation markers as well as the mesenchymal milieu including angiogenesis and infiltrate Our bioengineered skin based system represents a robust platform to reliably assess the molecular and cellular mechanisms underlying the complex interdependence between epidermal cells and the immune system The system may also prove suitable to assess preclinical studies that test the efficacy of novel therapeutic treatments and to predict individual patient response to therapy (Am J Pathol 2010 177 3112-3124, DOI 10 2353/ajpath 2010.100078)