Human plasmacytoid dentritic cells elicit a Type I Interferon response by sensing DNA via the cGAS-STING signaling pathway.
Human plasmacytoid dentritic cells elicit a Type I Interferon response by sensing DNA via the cGAS-STING signaling pathway.
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人浆细胞类动物的齿状细胞通过通过CGAS刺信信号通路传感DNA引起I型干扰素反应。
DOI：
10.1002/eji.201546113
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发表时间：
2016-07
影响因子：
5.4
通讯作者：
Steinhagen F
中科院分区：
文献类型：
--
作者：
Bode C;Fox M;Tewary P;Steinhagen A;Ellerkmann RK;Klinman D;Baumgarten G;Hornung V;Steinhagen F
浆细胞样树突状细胞（pDC）是I型干扰素（IFN）的主要来源，并且通过TLR 9感测微生物DNA而对宿主防御是重要的。pDC还在IFN驱动的自身免疫性疾病的发病机制中起关键作用。然而，这种自身免疫反应是由自身DNA的识别引起的，并且与TLR 9非依赖性途径有关。越来越多的证据表明，细胞溶质DNA受体环GMP-AMP（cGAMP）合酶（cGAS）是检测病原体的关键组分，并导致自身免疫性疾病。研究表明，DNA与cGAS的结合会导致cGAMP的合成，并随后激活干扰素基因刺激因子（STING）衔接子以诱导IFN。我们的结果显示cGAS-STING途径在人pDC中通过胞质DNA表达和活化，导致稳健的I型IFN应答。通过包括cGAMP的环状二核苷酸直接活化STING也活化pDC，并且STING的敲低消除了这种IFN应答。这些结果表明pDC通过cGAS-STING途径感测胞质DNA和环状二核苷酸，并且靶向该途径可能具有治疗意义。
Plasmacytoid dendritic cells (pDCs) are a major source of type I interferon (IFN) and are important for host defense by sensing microbial DNA via TLR9. pDCs also play a critical role in the pathogenesis of IFN-driven autoimmune diseases. Yet, this autoimmune reaction is caused by the recognition of self-DNA and has been linked to TLR9-independent pathways. Increasing evidence suggests that the cytosolic DNA receptor cyclic GMP-AMP (cGAMP) synthase (cGAS) is a critical component in the detection of pathogens and contributes to autoimmune diseases. It has been shown that binding of DNA to cGAS results in the synthesis of cGAMP and the subsequent activation of the stimulator of interferon genes (STING) adaptor to induce IFNs. Our results show that the cGAS-STING pathway is expressed and activated in human pDCs by cytosolic DNA leading to a robust type I IFN response. Direct activation of STING by cyclic dinucleotides including cGAMP also activated pDCs and knockdown of STING abolished this IFN response. These results suggest that pDCs sense cytosolic DNA and cyclic dinucleotides via the cGAS-STING pathway and that targeting this pathway could be of therapeutic interest.
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DOI：
10.1126/science.1244040
发表时间：
2013-09-20
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Li XD;Wu J;Gao D;Wang H;Sun L;Chen ZJ
通讯作者：
Chen ZJ
DOI：
10.1084/jem.20051654
发表时间：
2005-11-21
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Okabe Y;Kawane K;Akira S;Taniguchi T;Nagata S
通讯作者：
Nagata S
影响因子：
4.4
作者：
Decker, P;Singh-Jasuja, H;Rammensee, HG
通讯作者：
Rammensee, HG
IRF-5和NF-κBP50在TLR9刺激人浆细胞类树突状细胞中共调节IFN-β和IL-6表达。
影响因子：
5.4
作者：
Steinhagen F;McFarland AP;Rodriguez LG;Tewary P;Jarret A;Savan R;Klinman DM
通讯作者：
Klinman DM
影响因子：
5.4
作者：
Jung, Andreas;Kato, Hiroki;Akira, Shizuo
通讯作者：
Akira, Shizuo