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

• Published in: Nature immunology Vol. 16; no. 9; pp. 970 - 979
• Main Authors: Meller, Stephan, Di Domizio, Jeremy, Voo, Kui S, Friedrich, Heike C, Chamilos, Georgios, Ganguly, Dipyaman, Conrad, Curdin, Gregorio, Josh, Le Roy, Didier, Roger, Thierry, Ladbury, John E, Homey, Bernhard, Watowich, Stanley, Modlin, Robert L, Kontoyiannis, Dimitrios P, Liu, Yong-Jun, Arold, Stefan T, Gilliet, Michel
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.09.2015; Nature Publishing Group
• Subjects: 13/21; 14/19; 631/250/2499; 631/250/38; 692/420/256/2515; Biomedicine; Deoxyribonucleic acid; DNA; Immunology; Infectious Diseases
• ISSN: 1529-2908; 1529-2916
• DOI: 10.1038/ni.3211

T H 17 cells have important roles at mucosal surfaces in both health and disease. Gilliet and colleagues show that IL-26 is preferentially produced by human T H 17 cells and that this cytokine has both alarmin and direct antimicrobial functions. Interleukin 17–producing helper T cells (T H 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 H 17 cell–derived cytokine, is a cationic amphipathic protein that kills extracellular bacteria via membrane-pore formation. Furthermore, T H 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 H 17 cells by showing that IL-26 is a natural human antimicrobial that promotes immune sensing of bacterial and host cell death.