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Imiquimod-induced ex vivo model of psoriatic human skin via interleukin-17A signalling of T cells and Langerhans cells.
Carlos, Eduarda Cristina da Silva; Cristovão, Gabrielly Alves; Silva, Alcimar Alves; Ribeiro, Bianca Cristina de Santos; Romana-Souza, Bruna.
Afiliação
  • Carlos ECDS; Department of Histology and Embryology, Rio de Janeiro State University, Rio de Janeiro, Brazil.
  • Cristovão GA; Department of Histology and Embryology, Rio de Janeiro State University, Rio de Janeiro, Brazil.
  • Silva AA; Department of Histology and Embryology, Rio de Janeiro State University, Rio de Janeiro, Brazil.
  • Ribeiro BCS; Department of Histology and Embryology, Rio de Janeiro State University, Rio de Janeiro, Brazil.
  • Romana-Souza B; Department of Histology and Embryology, Rio de Janeiro State University, Rio de Janeiro, Brazil.
Exp Dermatol ; 31(11): 1791-1799, 2022 11.
Article em En | MEDLINE | ID: mdl-36054147
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Psoríase / Células de Langerhans Limite: Animals / Humans Idioma: En Revista: Exp Dermatol Assunto da revista: DERMATOLOGIA Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Brasil País de publicação: Dinamarca

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Psoríase / Células de Langerhans Limite: Animals / Humans Idioma: En Revista: Exp Dermatol Assunto da revista: DERMATOLOGIA Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Brasil País de publicação: Dinamarca