Infiltration of T Cells into a Three-Dimensional Psoriatic Skin Model Mimics Pathological Key Features

Abstract

Psoriasis is an autoimmune chronic dermatosis that is T cell-mediated, characterized by epidermal thickening, aberrant epidermal differentiation and inflammatory infiltrates, with a dominant Th1 and Th17 profile. Additional in vitro models are required to study the complex interactions between activated T cells and skin cells, and to develop new, more effective treatments. We have therefore sought to model this psoriatic inflammation by the generation of tissue-engineered immunocompetent tissues, and we have investigated the response of activated T-cell infiltration in models produced with lesional psoriatic skin cells on major hallmarks of psoriasis. The immunocompetent lesional skin model displayed a delayed onset of epidermal differentiation, an hyperproliferation of the basal keratinocytes, a drastic increase in the secretion of proinflammatory cytokines, and a disturbed expression of key transcription factors, as observed in lesional plaques, suggesting a crucial importance of combining the pathological phenotype of cutaneous cells to T cells in order to generate a relevant model for psoriasis. Finally, we found this skin model to be responsive to methotrexate treatment, making it a valuable tool for drug development.