Epigenetic control of IL-23 expression in keratinocytes is important for chronic skin inflammation.
Nat Commun
; 9(1): 1420, 2018 04 12.
Article
em En
| MEDLINE
| ID: mdl-29650963
ABSTRACT
The chronic skin inflammation psoriasis is crucially dependent on the IL-23/IL-17 cytokine axis. Although IL-23 is expressed by psoriatic keratinocytes and immune cells, only the immune cell-derived IL-23 is believed to be disease relevant. Here we use a genetic mouse model to show that keratinocyte-produced IL-23 is sufficient to cause a chronic skin inflammation with an IL-17 profile. Furthermore, we reveal a cell-autonomous nuclear function for the actin polymerizing molecule N-WASP, which controls IL-23 expression in keratinocytes by regulating the degradation of the histone methyltransferases G9a and GLP, and H3K9 dimethylation of the IL-23 promoter. This mechanism mediates the induction of IL-23 by TNF, a known inducer of IL-23 in psoriasis. Finally, in keratinocytes of psoriatic lesions a decrease in H3K9 dimethylation correlates with increased IL-23 expression, suggesting relevance for disease. Taken together, our data describe a molecular pathway where epigenetic regulation of keratinocytes can contribute to chronic skin inflammation.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Psoríase
/
Pele
/
Histona-Lisina N-Metiltransferase
/
Epigênese Genética
/
Proteína Neuronal da Síndrome de Wiskott-Aldrich
/
Subunidade p19 da Interleucina-23
Limite:
Adult
/
Animals
/
Humans
/
Male
/
Middle aged
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article