Epigenetic Control of IL-23 Expression in Keratinocytes is Important for Chronic Skin Inflammation

Overview

Journal Nat Commun

Specialty Biology

Date 2018 Apr 14

PMID 29650963

Citations 61

Authors

Hui Li

Qi Yao

Alberto Garcia Mariscal

Xudong Wu

Justus Hulse

Esben Pedersen

Kristian Helin

Ari Waisman

Caroline Vinkel

Simon Francis Thomsen

Alexandra Avgustinova

Salvador Aznar Benitah

Paola Lovato

Hanne Norsgaard

Mette Sidsel Mortensen

Lone Veng

Bjorn Rozell

Cord Brakebusch

Affiliations

Soon will be listed here.

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.

Citing Articles

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