T<inf>H</inf>17 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

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Abstract

Interleukin 17-producing helper T cells (T<inf>H</inf> 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 T<inf>H</inf>17 cell-derived cytokine, is a cationic amphipathic protein that kills extracellular bacteria via membrane-pore formation. Furthermore, T<inf>H</inf>17 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 T<inf>H</inf>17 cells by showing that IL-26 is a natural human antimicrobial that promotes immune sensing of bacterial and host cell death.

Original languageEnglish (US)
Pages (from-to)970-979
Number of pages10
JournalNature Immunology
Volume16
Issue number9
DOIs
StatePublished - Aug 19 2015

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ASJC Scopus subject areas

  • Immunology

Cite this

Meller, S., Di Domizio, J., Voo, K. S., Friedrich, H. C., Chamilos, G., Ganguly, D., Conrad, C., Gregorio, J., Le Roy, D., Roger, T., Ladbury, J. E., Homey, B., Watowich, S., Modlin, R. L., Kontoyiannis, D. P., Liu, Y. J., Arold, S. T., & Gilliet, M. (2015). T<inf>H</inf>17 cells promote microbial killing and innate immune sensing of DNA via interleukin 26. Nature Immunology, 16(9), 970-979. https://doi.org/10.1038/ni.3211