Langerhans cell markers CD1a and CD207 are the most rapidly responding genes in lesional psoriatic skin following adalimumab treatment

• Published in: Experimental 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
• Language: English
• Published: Denmark Wiley Subscription Services, Inc 01-09-2017
• Subjects: Adalimumab - pharmacology; Adalimumab - therapeutic use; Adult; Aged; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Antigens, CD - metabolism; Antigens, CD1 - metabolism; biological therapy; Cell Movement; Culture Techniques; cytokines; Dermatologic Agents - pharmacology; Dermatologic Agents - therapeutic use; Dermis; Drug delivery; Epidermis; ex vivo skin model; FDA approval; Female; Gene expression; Humans; Immunotherapy; Interleukin 17; Interleukin 23; Langerhans cells; Langerhans Cells - drug effects; Langerhans Cells - metabolism; Lectins, C-Type - metabolism; Mannose-Binding Lectins - metabolism; Middle Aged; Monoclonal antibodies; Psoriasis; Psoriasis - drug therapy; Psoriasis - metabolism; Skin - cytology; Skin - drug effects; Skin - metabolism; Skin diseases; Studies; Tumor Necrosis Factor-alpha; Ustekinumab - pharmacology; Ustekinumab - therapeutic use; cytokines; ex vivo skin model; biological therapy; psoriasis
• ISSN: 0906-6705; 1600-0625
• DOI: 10.1111/exd.13304

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.