Article open access publication

Epigenetic control of IL-23 expression in keratinocytes is important for chronic skin inflammation

Nature Communications, Springer Nature, ISSN 2041-1723

Volume 9, 1, 2018

DOI:10.1038/s41467-018-03704-z, Dimensions: pub.1103149442, PMC: PMC5897363, PMID: 29650963,

Affiliations

Organisations

  1. (1) University of Copenhagen, grid.5254.6, KU
  2. (2) Centre for Epigenetics, Ole Maaløes Vej 5, 2200, Copenhagen, Denmark
  3. (3) Johannes Gutenberg University of Mainz, grid.5802.f
  4. (4) Bispebjerg Hospital, grid.411702.1, Capital Region
  5. (5) Catalan Institution for Research and Advanced Studies, grid.425902.8
  6. (6) Institute for Research in Biomedicine, grid.7722.0
  7. (7) Leo Pharma (Denmark), grid.420009.f

Countries

Denmark

Spain

Germany

Continents

Europe

Description

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.

Funders

Research Categories

Main Subject Area

Fields of Research

Links & Metrics

NORA University Profiles

University of Copenhagen

Danish Open Access Indicator

2018: Realized

Research area: Medicine

Danish Bibliometrics Indicator

2018: Level 2

Research area: Medicine

Dimensions Citation Indicators

Times Cited: 24

Field Citation Ratio (FCR): 8.08

Relative Citation ratio (RCR): 2.58

Open Access Info

Pure Gold