TH17 cells promote microbial killing and innate immune sensing of DNA via interleukin 26

Stephan Meller, Jeremy Di Domizio, Kui S Voo, Heike C Friedrich, Georgios Chamilos, Dipyaman Ganguly, Curdin Conrad, Josh Gregorio, Didier Le Roy, Thierry Roger, John E Ladbury, Bernhard Homey, Stanley Watowich, Robert L Modlin, Dimitrios P Kontoyiannis, Yong-Jun Liu, Stefan T. Arold, Michel Gilliet

Research output: Contribution to journalArticlepeer-review

123 Scopus citations

Abstract

Interleukin 17-producing helper T cells (TH 17 cells) have a major role in protection against infections and in mediating autoimmune diseases, yet the mechanisms involved are incompletely understood. We found that interleukin 26 (IL-26), a human TH17 cell-derived cytokine, is a cationic amphipathic protein that kills extracellular bacteria via membrane-pore formation. Furthermore, TH17 cell-derived IL-26 formed complexes with bacterial DNA and self-DNA released by dying bacteria and host cells. The resulting IL-26-DNA complexes triggered the production of type I interferon by plasmacytoid dendritic cells via activation of Toll-like receptor 9, but independently of the IL-26 receptor. These findings provide insights into the potent antimicrobial and proinflammatory function of TH17 cells by showing that IL-26 is a natural human antimicrobial that promotes immune sensing of bacterial and host cell death. © 2015 Nature America, Inc.
Original languageEnglish (US)
Pages (from-to)970-979
Number of pages10
JournalNature Immunology
Volume16
Issue number9
DOIs
StatePublished - Jul 13 2015

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