Cytosolic DNA triggers inflammasome activation in keratinocytes in psoriatic lesions

Yvonne Dombrowski, Mark Peric, Sarah Koglin, Claudia Kammerbauer, Christine Göss, David Anz, Maren Simanski, Regine Gläser, Jürgen Harder, Veit Hornung, Richard L Gallo, Thomas Ruzicka, Robert Besch, Jürgen Schauber

Research output: Contribution to journalArticlepeer-review

265 Citations (Scopus)

Abstract

The proinflammatory cytokine interleukin-1β (IL-1β) plays a central role in the pathogenesis and the course of inflammatory skin diseases, including psoriasis. Posttranscriptional activation of IL-1β is mediated by inflammasomes; however, the mechanisms triggering IL-1β processing remain unknown. Recently, cytosolic DNA has been identified as a danger signal that activates inflammasomes containing the DNA sensor AIM2. In this study, we detected abundant cytosolic DNA and increased AIM2 expression in keratinocytes in psoriatic lesions but not in healthy skin. In cultured keratinocytes, interferon-γ induced AIM2, and cytosolic DNA triggered the release of IL-1β via the AIM2 inflammasome. Moreover, the antimicrobial cathelicidin peptide LL-37, which can interact with DNA in psoriatic skin, neutralized cytosolic DNA in keratinocytes and blocked AIM2 inflammasome activation. Together, these data suggest that cytosolic DNA is an important disease-associated molecular pattern that can trigger AIM2 inflammasome and IL-1β activation in psoriasis. Furthermore, cathelicidin LL-37 interfered with DNA-sensing inflammasomes, which thereby suggests an anti-inflammatory function for this peptide. Thus, our data reveal a link between the AIM2 inflammasome, cathelicidin LL-37, and autoinflammation in psoriasis, providing new potential targets for the treatment of this chronic skin disease.
Original languageEnglish
Pages (from-to)82ra38
JournalScience Translational Medicine
Volume3
Issue number82
DOIs
Publication statusPublished - 11 May 2011

Keywords

  • Cathelicidins
  • Cytosol
  • DNA
  • Humans
  • Inflammasomes
  • Interleukin-1beta
  • Keratinocytes
  • Nuclear Proteins
  • Protein Binding
  • Psoriasis

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