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.

Langerhans Cells: Sensing the Environment in Health and Disease

“…These authors demonstrate that Langerin + cells can enhance DMBA-induced DNA damage, although in light of recent findings, it remains to be established whether the LCs are the main Langerin + DCs that are capable of metabolizing DMBA. Indeed, various reports now show that the DMBA-metabolizing activity of LCs is dispensable for inflicting H-Ras mutations in keratinocytes ( 120 , 121 ).…”

Human Langerhans Cells with Pro-inflammatory Features Relocate within Psoriasis Lesions

“…Reduced migration of LCs toward inflammatory cytokines is attributed to the IL-17-induced keratinocyte secretome ( 77 ). A possible consequence of this migrational impairment is the accumulation of LCs in the dermis ( 67 , 78 – 82 ), where they form dermal aggregates with T cells outside lymphatic vessels (Figures 2 A–C). The localization of LCs in dermis and basal epidermis, adjacent to the basement membrane in areas where dermal immune cells are entering the epidermis, raises questions on the nature of interactions between LCs and other inflammatory cells, questions that at large remain to be answered.…”

Langerhans cells in psoriasis: getting to the core of the disease

“…5 The expression of the genes that code for CD1a and CD207 are downregulated early in successful treatment of psoriasis with adalimumab. 6 Studies in the imiquimod mouse model of psoriasis have suggested that dendritic cells including Langerhans cells are essential for the development of psoriasis-like inflammation. 7 The study by Eaton et al in this issue of the BJD builds on previous work from this group.…”