Langerhans cell markers CD 1a and CD 207 are the most rapidly responding genes in lesional psoriatic skin following adalimumab treatment

Abstract TNF α‐, 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 ( LC s) is reduced, but the role of LC is poorly understood. The purpose of this study...

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Published inExperimental dermatology Vol. 26; no. 9; pp. 804 - 810
Main Authors Raaby, Line, Rosada, Cecilia, Langkilde, Ane, Lauridsen, Kristina Lystlund, Vinter, Hanne, Ommen, Pernille, Kjellerup, Rasmus Boye, Johansen, Claus, Iversen, Lars
Format Journal Article
LanguageEnglish
Published 01.09.2017
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Abstract Abstract TNF α‐, 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 ( LC s) is reduced, but the role of LC is poorly understood. The purpose of this study was to investigate the impact of TNF α 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, TNF α 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, CD 1a and CD 207, were among the most up‐ or downregulated genes in psoriatic skin after anti‐ TNF α 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 CD 1a level was seen after TNF α 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, TNF α 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.
AbstractList Abstract TNF α‐, 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 ( LC s) is reduced, but the role of LC is poorly understood. The purpose of this study was to investigate the impact of TNF α 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, TNF α 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, CD 1a and CD 207, were among the most up‐ or downregulated genes in psoriatic skin after anti‐ TNF α 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 CD 1a level was seen after TNF α 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, TNF α 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.
Author Iversen, Lars
Lauridsen, Kristina Lystlund
Johansen, Claus
Raaby, Line
Vinter, Hanne
Kjellerup, Rasmus Boye
Ommen, Pernille
Langkilde, Ane
Rosada, Cecilia
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Title Langerhans cell markers CD 1a and CD 207 are the most rapidly responding genes in lesional psoriatic skin following adalimumab treatment
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