title: Langerhans cell markers CD1a and CD207 are the most rapidly responding genes in lesional psoriatic skin following adalimumab treatment.
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.
authors.affiliation: Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark.|Department of Pathology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Line
authors.identifier: 0000-0002-3327-9613
authors.initials: L
authors.lastname: Raaby
authors.affiliation: Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Rosada
authors.affiliation: Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Ane
authors.initials: A
authors.lastname: Langkilde
authors.affiliation: Department of Pathology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Kristina Lystlund
authors.initials: KL
authors.lastname: Lauridsen
authors.affiliation: Department of Pathology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Hanne
authors.initials: H
authors.lastname: Vinter
authors.affiliation: Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Pernille
authors.initials: P
authors.lastname: Ommen
authors.affiliation: Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Rasmus Boye
authors.initials: RB
authors.lastname: Kjellerup
authors.affiliation: Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Claus
authors.initials: C
authors.lastname: Johansen
authors.affiliation: Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Lars
authors.initials: L
authors.lastname: Iversen
mesh_terms: D000068879:Adalimumab / Q000494:pharmacology / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015703:Antigens, CD / Q000378:metabolism; D018949:Antigens, CD1 / Q000378:metabolism; D002465:Cell Movement; D046508:Culture Techniques; D003879:Dermatologic Agents / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007801:Langerhans Cells / Q000187:drug effects* / Q000378:metabolism; D037181:Lectins, C-Type / Q000378:metabolism; D037241:Mannose-Binding Lectins / Q000378:metabolism; D008875:Middle Aged; D011565:Psoriasis / Q000188:drug therapy* / Q000378:metabolism; D012867:Skin / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha; D000069549:Ustekinumab / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000893:Anti-Inflammatory Agents; D015703:Antigens, CD; D018949:Antigens, CD1; C419393:CD1a antigen; C121916:CD207 protein, human; D003879:Dermatologic Agents; D037181:Lectins, C-Type; D037241:Mannose-Binding Lectins; D014409:Tumor Necrosis Factor-alpha; D000069549:Ustekinumab; D000068879:Adalimumab
keywords: biological therapy; cytokines; ex vivo skin model; psoriasis