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.
Highlights
Psoriasis is a T-cell mediated autoimmune disease associated with three main characteristics: Aberrant growth and hyperproliferation of epidermal keratinocytes, altered epithelial differentiation, and leukocyte infiltration, causing secretion of inflammatory mediators [1,2]
We developed an immunocompetent in vitro lesional skin model to mimic the infiltration of activated T cells observable in vivo in psoriatic lesion plaques
This study demonstrates that psoriatic keratinocytes show in vitro a delayed onset of epidermal differentiation, as already demonstrated by Bernerd et al in 1992 [26], highlighting the abnormality of the basal layer
Summary
Psoriasis is a T-cell mediated autoimmune disease associated with three main characteristics: Aberrant growth and hyperproliferation of epidermal keratinocytes, altered epithelial differentiation, and leukocyte infiltration, causing secretion of inflammatory mediators [1,2]. The proven clinical efficacy of drugs to inhibit or block the immune system, lymphocyte-induced secretions, demonstrates the importance of T cells in the development and maintenance of the pathology [5,6,7,8]. Evidence of the importance of T cell-induced inflammatory cytokines is abundant. Van den Bogaard et al developed a dermal equivalent model composed of a decellularized and deepidermized dermis, on which healthy keratinocytes are seeded, and activated CD4-positive cells are injected [10]
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