Epigenetic control of IL-23 expression in keratinocytes is important for chronic skin inflammation
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- Epigenetic control of IL-23 expression in keratinocytes is important for chronic skin inflammation
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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.
Originalsprog | Engelsk |
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Artikelnummer | 1420 |
Tidsskrift | Nature Communications |
Vol/bind | 9 |
Udgave nummer | 1 |
Sider (fra-til) | 1-18 |
Antal sider | 18 |
ISSN | 2041-1723 |
DOI | |
Status | Udgivet - 2018 |
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ID: 199320903