Impaired Langerhans’ cell migration in psoriasis is due to an altered keratinocyte phenotype induced by interleukin-17

Abstract

Psoriasis is a common skin condition driven by increased expression of interleukin (IL)-17. Langerhans' cells (LC) are epidermal dendritic cells that regulate cutaneous immune responses. Within uninvolved skin of patients with psoriasis, LC display impaired migration from the epidermis. Here the role of keratinocytes (KC) in the regulation of LC function, and the response of KC to IL-17 has been investigated. Keratinocytes were cultured from the uninvolved skin of psoriasis patients and healthy individuals with or without IL-17 treatment and the conditioned medium examined for its ability to alter LC function in an ex vivo human skin explant model. Furthermore, we examined the effect of IL-17 on LC mobilisation in psoriasis by neutralising IL-17 in the same skin explant model. We found that conditioned medium from psoriasis KC inhibited LC migration in healthy skin. Moreover, conditioned medium from healthy KC treated with IL-17 also inhibited healthy LC migration. Finally, neutralising IL-17 in psoriasis skin resulted in enhanced LC migration. Collectively, these data suggest that an altered KC secretome, driven by increased expression of IL-17, is responsible for impaired LC migration in uninvolved skin of patients with psoriasis.

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