T(H)17 cells promote microbial killing and innate immune sensing of DNA via interleukin 26.
T(H)17 cells promote microbial killing and innate immune sensing of DNA via interleukin 26.
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DOI：
10.1038/ni.3211
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发表时间：
2015-09
影响因子：
30.5
通讯作者：
Gilliet M
中科院分区：
文献类型：
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作者：
Meller S;Di Domizio J;Voo KS;Friedrich HC;Chamilos G;Ganguly D;Conrad C;Gregorio J;Le Roy D;Roger T;Ladbury JE;Homey B;Watowich S;Modlin RL;Kontoyiannis DP;Liu YJ;Arold ST;Gilliet M
产生白细胞介素17的辅助性T细胞（TH17细胞）在预防感染和介导自身免疫性疾病中发挥重要作用，但其机制尚不完全清楚。我们发现白细胞介素26 （IL-26）是一种人类TH17细胞衍生的细胞因子，是一种阳离子两性蛋白，通过膜孔形成杀死细胞外细菌。此外，TH17细胞衍生的IL-26与垂死细菌和宿主细胞释放的细菌DNA和自身DNA形成复合物。由此产生的IL-26 - dna复合物通过激活toll样受体9触发浆细胞样树突状细胞产生I型干扰素，但不依赖于IL-26受体。这些发现通过表明IL-26是一种天然的人类抗菌素，促进对细菌和宿主细胞死亡的免疫感知，为TH17细胞的有效抗菌和促炎功能提供了见解。
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.