Th17 cells promote microbial killing and innate immune sensing of DNA via IL-26

S. Meller, J. Di Domizio, K.S. Voo, H.C. Friedrich, G. Chamilos, D. Ganguly, C. Conrad, J. Gregorio, D. Le Roy, T. Roger, J.E. Ladbury, B. Homey, S. Watowich, R.L. Modlin, D.P. Kontoyiannis, Y.J. Liu, S.T. Arold, M. Gilliet
Nat. Immunology, 16(9), 970-9, (2015)

Th17 cells promote microbial killing and innate immune sensing of DNA via IL-26

Keywords

TH17 cellderived cytokine, Interleukin 26 (IL-26), DNA

Abstract

​Interleukin 17–producing helper T cells (TH17 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.

Code

DOI: 10.1038/ni.3211

Sources

Website PDF

See all publications 2015