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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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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CitedBy_id | crossref_primary_10_1111_exd_14549 crossref_primary_10_3390_jpm12122072 crossref_primary_10_14814_phy2_15604 crossref_primary_10_1111_bjd_16596 crossref_primary_10_3389_fimmu_2018_00300 crossref_primary_10_1093_ced_llae006 crossref_primary_10_2147_CCID_S412162 crossref_primary_10_1016_j_phrs_2019_104473 crossref_primary_10_1016_j_jid_2021_01_005 crossref_primary_10_3389_fimmu_2018_00093 crossref_primary_10_1111_exd_13942 |
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TNF
α‐,
IL
‐23‐ and
IL
‐17‐targeting drugs are highly effective in the treatment of psoriasis. However, the precise molecular mechanism remains... |
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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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