T(H)17 cells promote microbial killing and innate immune sensing of DNA via interleukin 26.
Stephan MellerJeremy Di DomizioKui S VooHeike C FriedrichGeorgios ChamilosDipyaman GangulyCurdin ConradJosh GregorioDidier Le RoyThierry RogerJohn E LadburyBernhard HomeyStanley WatowichRobert L ModlinDimitrios P KontoyiannisYong-Jun LiuStefan T AroldMichel GillietPublished in: Nature immunology (2015)
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.
Keyphrases
- dendritic cells
- induced apoptosis
- cell cycle arrest
- cell death
- toll like receptor
- circulating tumor
- endothelial cells
- cell free
- single molecule
- immune response
- endoplasmic reticulum stress
- regulatory t cells
- palliative care
- innate immune
- cell proliferation
- microbial community
- binding protein
- nuclear factor
- nucleic acid
- small molecule
- protein protein
- circulating tumor cells