IL-29 is produced by T(H)17 cells and mediates the cutaneous antiviral competence in psoriasis.
Sci Transl Med
; 5(204): 204ra129, 2013 Sep 25.
Article
em En
| MEDLINE
| ID: mdl-24068736
ABSTRACT
Psoriasis and atopic dermatitis (AD) are the most common chronic inflammatory skin diseases. Although both patient groups show strongly impaired skin barrier function, only AD patients frequently suffer from cutaneous viral infections. The mechanisms underlying the distinct susceptibilities to these pathogenetic and often life-threatening infections are unknown. We show that antiviral proteins (AVPs) such as MX1, BST2, ISG15, and OAS2 were strongly elevated in psoriatic compared to AD lesions and healthy skin. Of 30 individually quantified cytokines in psoriatic lesions, interleukin-29 (IL-29) was the only mediator whose expression correlated with the AVP levels. IL-29 was absent in AD lesions, and neutralization of IL-29 in psoriatic skin reduced AVP expression. Accordingly, IL-29 raised AVP levels in isolated keratinocytes, epidermis models, and human skin explants, but did not influence antibacterial protein production. AVP induction correlated with increased antiviral defense of IL-29-treated keratinocytes. Furthermore, IL-29 elevated the expression of signaling elements, resulting in increased sensitivity of keratinocytes toward its own action. We identified T helper 17 (T(H)17) cells as IL-29 producers and demonstrated their ability to increase the antiviral competence of keratinocytes in an IL-29-dependent manner. Transforming growth factor-ß and the activity of RORγt/RORα were most critical for the development of IL-29-producing T(H)17 cells. IL-29 secretion by these cells was dependent on NFAT and c-Jun N-terminal kinase and was inhibited by IL-4. These data suggest that T(H)17 cell-derived IL-29, which is absent in AD, mediates the robust antiviral state on psoriatic skin, and demonstrate a new function of T(H)17 cells.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Psoríase
/
Pele
/
Interleucinas
/
Células Th17
Tipo de estudo:
Prognostic_studies
Limite:
Adult
/
Humans
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article