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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Nat+Commun
2018 ; 9
(1
): 1420
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Epigenetic control of IL-23 expression in keratinocytes is important for chronic
skin inflammation
#MMPMID29650963
Li H
; Yao Q
; Mariscal AG
; Wu X
; Hülse J
; Pedersen E
; Helin K
; Waisman A
; Vinkel C
; Thomsen SF
; Avgustinova A
; Benitah SA
; Lovato P
; Norsgaard H
; Mortensen MS
; Veng L
; Rozell B
; Brakebusch C
Nat Commun
2018[Apr]; 9
(1
): 1420
PMID29650963
show ga
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.