Assuntos
Receptores de N-Metil-D-Aspartato/metabolismo , Pele/metabolismo , Estresse Psicológico/metabolismo , Doença Aguda , Adulto , Método Duplo-Cego , Feminino , Expressão Gênica , Voluntários Saudáveis , Humanos , Masculino , Projetos Piloto , Análise Serial de Proteínas/métodos , Receptores de N-Metil-D-Aspartato/genética , Estresse Psicológico/genéticaRESUMO
BACKGROUND: 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. OBJECTIVES: To investigate the role of keratinocytes (KCs) in the regulation of LC function and the response of KCs to IL-17. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.