Imiquimod-induced ex vivo model of psoriatic human skin via interleukin-17A signalling of T cells and Langerhans cells.

Abstract

Several in vitro models have been developed to study the mechanisms involved in psoriasis and to screen new antipsoriatic drugs. However, most of them use single-cell or reconstructed human skin models that did not have complex anatomy of human skin. Thus, this study aimed to create a new model of psoriasis-like dermatitis using human skin under in vitro conditions. To perform this, human skin explants were topically treated with imiquimod (IMQ) or vehicle for 2, 3 or 6 consecutive days. Some explants were treated with an anti-psoriatic drug or antibody anti-interleukin-17A (IL-17A). Topical application of IMQ increased total epidermal area, epidermal proliferation and keratinocyte differentiation at 3, 4 or 7 days. The protein levels of CD3 were augmented in the IMQ-treated human skin explants at 7 days reflecting the activation of T cells. Topical IMQ promoted a higher protein and mRNA levels of IL-17A in human skin ex vivo. Immunofluorescence analysis showed CD207-positive Langerhans cells (LCs) and CD3-positive T cells expressing IL-17A in IMQ-treated human skin explants at 7 days. In addition, administration of antibody anti-IL-17A or an anti-psoriatic drug inhibited IMQ-induced increase in the epidermal thickness in ex vivo human skin at 7 days. In conclusion, topical IMQ application promotes epidermal changes in ex vivo human skin that resemble to human psoriatic skin lesions. Moreover, IMQ-induced production of IL-17 by LCs and T cells is critical to development of psoriasis-like inflammation in our model. This new model is suitable for in vitro screening of antipsoriatic drugs.