IL-17 and IL-22 enhance skin inflammation by stimulating the secretion of il-1β by keratinocytes via the ROS-NLRP3-caspase-1 pathway

Kyung Ah Cho, Jee Won Suh, Kyung Ho Lee, Jihee Lee Kang, So Youn Woo

Research output: Contribution to journalArticlepeer-review

107 Scopus citations

Abstract

Background: The pathogenesis of inflammatory skin disease involves the release of cytokines from keratinocytes, and one of these, IL-1β, has been previously implicated in inflammatory skin disease. Th17 cells, a subset of Th cells involved in autoimmunity and inflammation, possess IL-1β receptors and secrete cytokines such as IL-17 and IL-22 in response to IL-1β stimulation. A mutation in the inflammasome protein NLRP3 (NACHT, LRR and PYD domains-containing protein 3) causes excess production of IL-1β, resulting in an augmentation of Th17-dominant pathology. Methods: To determine the feedback effect, if any, of IL-17 and/or IL-22 on the secretion of IL-1β from keratinocytes, we stimulated the human keratinocyte cell line HaCaT, as well as caspase-1-deficient mice, with IL-17 or IL-22. Results: We found that treatment with IL-17 and IL-22 causes an increase in IL-1β via the activation of NLRP3 by a process that involves the generation of reactive oxygen species. Moreover, skin inflammation induced by IL-17 and IL-22 was lower in caspase-1 knockout (KO) mice relative to that induced by IL-1β treatment. Additionally, skin inflammation induced by the drug imiquimod was lower in caspase-1 KO mice than in wild-type mice. Conclusion: These results indicate that cytokines from Th17 cells may potentiate IL-1β-mediated skin inflammation and result in phenotypic alterations of keratinocytes via a feedback mechanism.

Original languageEnglish
Pages (from-to)147-158
Number of pages12
JournalInternational Immunology
Volume24
Issue number3
DOIs
StatePublished - Mar 2012

Keywords

  • HaCaT cells
  • Imiquimod
  • Inflammasome

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