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 in | Experimental dermatology Vol. 26; no. 9; pp. 804 - 810 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
01.09.2017
|
Online Access | Get full text |
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Summary: | 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. |
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ISSN: | 0906-6705 1600-0625 |
DOI: | 10.1111/exd.13304 |