The Department of Biomedicine

CCBIO seminar: Cord Brakebusch

Epigenetic control of skin inflammation

Cord Brakebusch
Biotech Research and Innovation Center (BRIC), University of Copenhagen, Denmark

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. Using a genetic mouse model we now 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, these data describe a molecular pathway where epigenetic regulation of keratinocytes can contribute to chronic skin inflammation.

Chairperson: Donald Gullberg, CCBIO