Epithelial TRAF6 drives IL-17-mediated psoriatic inflammation.
JCI Insight
; 3(15)2018 08 09.
Article
em En
| MEDLINE
| ID: mdl-30089718
ABSTRACT
Epithelial cells are the first line of defense against external dangers, and contribute to induction of adaptive immunity including Th17 responses. However, it is unclear whether specific epithelial signaling pathways are essential for the development of robust IL-17-mediated immune responses. In mice, the development of psoriatic inflammation induced by imiquimod required keratinocyte TRAF6. Conditional deletion of TRAF6 in keratinocytes abrogated dendritic cell activation, IL-23 production, and IL-17 production by γδ T cells at the imiquimod-treated sites. In contrast, hapten-induced contact hypersensitivity and papain-induced IgE production were not affected by loss of TRAF6. Loss of psoriatic inflammation was not solely due to defective imiquimod sensing, as subcutaneous administration of IL-23 restored IL-17 production but did not reconstitute psoriatic pathology in the mutant animals. Thus, TRAF6 was required for the full development of IL-17-mediated inflammation. Therefore, epithelial TRAF6 signaling plays an essential role in both triggering and propagating IL-17-mediated psoriatic inflammation.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Psoríase
/
Queratinócitos
/
Fator 6 Associado a Receptor de TNF
/
Linfócitos Intraepiteliais
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
JCI Insight
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Japão