1. Langerhans cell markers CD1a and CD207 are the most rapidly responding genes in lesional psoriatic skin following adalimumab treatment.
- Author
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Raaby, Line, Rosada, Cecilia, Langkilde, Ane, Lauridsen, Kristina Lystlund, Vinter, Hanne, Ommen, Pernille, Kjellerup, Rasmus Boye, Johansen, Claus, and Iversen, Lars
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LANGERHANS cells ,ADALIMUMAB ,MESSENGER RNA ,INTERLEUKIN-17 ,MONOCLONAL antibodies - Abstract
TNFα-, IL-23- and IL-17-targeting drugs are highly effective in the treatment of psoriasis. However, the precise molecular mechanism remains unknown. In psoriatic skin, the presence of Langerhans cells ( LCs) is reduced, but the role of LC is poorly understood. The purpose of this study was to investigate the impact of TNFα and IL-23/ IL-17 on the presence of LC in the skin during treatment. Therefore, psoriatic skin was investigated before and after 4 days of adalimumab or ustekinumab treatment. Furthermore, TNFα and IL-17A stimulation was investigated in an ex vivo model of epidermis and dermis from healthy normal skin kept in cultures at an air-liquid interphase for 4 days. In a gene array analysis, we found that the two LC markers, CD1a and CD207, were among the most up- or downregulated genes in psoriatic skin after anti- TNFα therapy. Validation showed that both mRNA expression and protein level followed the same pattern and became significantly upregulated after 4 days of treatment. No changes were seen after ustekinumab treatment. In the ex vivo skin model, a decrease in the CD1a level was seen after TNFα stimulation and it was caused by LC migration from epidermis. No response in LC migration was seen after IL-17A stimulation. Taken together, we demonstrated that changes in the LC level in epidermis precede the histological and clinical changes during adalimumab treatment in psoriatic skin. Furthermore, TNFα plays a prominent role in orchestrating LC migration in the skin. This seems not to be the true for the IL-23/ IL-17A pathway. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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