Journal Article

T(H)17 cells promote microbial killing and innate immune sensing of DNA via interleukin 26

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

2015

Overview

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.

• Subject: Animals / Dendritic Cells - immunology / Dendritic Cells - metabolism / DNA - immunology / DNA, Bacterial - immunology / Humans / Immunity, Innate - immunology / Interferon Type I - immunology / Interferon Type I - metabolism / Interleukins - immunology / Mice / Psoriasis - immunology / Receptors, Interleukin - immunology / Receptors, Interleukin - metabolism / Th17 Cells - immunology / Toll-Like Receptor 9 - immunology