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

Psoriasis is a common skin condition driven by increased expression of interleukin (IL)-17. Langerhans cells (LCs) are epidermal dendritic cells that regulate cutaneous immune responses. Within the uninvolved skin of patients with psoriasis, LCs display impaired migration from the epidermis.

To investigate the role of keratinocytes (KCs) in the regulation of LC function and the response of KCs to IL-17.

KCs were cultured from the uninvolved skin of patients with psoriasis 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 mobilization in psoriasis by neutralizing IL-17 in the same skin explant model.

Conditioned medium from psoriasis KCs inhibited LC migration in healthy skin. Moreover, conditioned medium from healthy KCs treated with IL-17 also inhibited healthy LC migration. Finally, neutralizing 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 the uninvolved skin of patients with psoriasis.