IRF-5 and NF-κB p50 co-regulate IFN-β and IL-6 expression in TLR9-stimulated human plasmacytoid dendritic cells.
IRF-5 and NF-κB p50 co-regulate IFN-β and IL-6 expression in TLR9-stimulated human plasmacytoid dendritic cells.
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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。
DOI：
10.1002/eji.201242792
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发表时间：
2013-07
影响因子：
5.4
通讯作者：
Klinman DM
中科院分区：
文献类型：
--
作者：
Steinhagen F;McFarland AP;Rodriguez LG;Tewary P;Jarret A;Savan R;Klinman DM
表达CpG基序的合成寡核苷酸（ODN）模拟细菌DNA通过TLR 9触发先天免疫系统的能力。浆细胞样树突状细胞（pDC）对随后的免疫应答做出关键贡献。本工作检查了CpG刺激的人pDC和人CAL-1 pDC细胞系对抗病毒（IFN-β）和促炎（IL-6）细胞因子的诱导。结果显示干扰素调节因子-5（IRF-5）和NF-κB p50是TLR 9介导的人pDC活化后IFN-β和IL-6表达的关键共调节因子。还观察到IRF-1的核蓄积，但这是依赖于1型IFN的晚期事件，与基因表达的起始无关。IRF-8被鉴定为CpG刺激的pDC中基因活化的新负调节剂。由于最近发现IRF-5和IRF-8的变体与某些自身免疫性疾病的易感性相关，这些发现与我们对“K”ODN的药理学作用以及TLR 9连接在生理、病理和治疗条件下的作用的理解相关。
Synthetic oligonucleotides (ODN) expressing CpG motifs mimic the ability of bacterial DNA to trigger the innate immune system via TLR9. Plasmacytoid dendritic cells (pDCs) make a critical contribution to the ensuing immune response. This work examines the induction of antiviral (IFN-β) and pro-inflammatory (IL-6) cytokines by CpG-stimulated human pDCs and the human CAL-1 pDC cell line. Results show that interferon regulatory factor-5 (IRF-5) and NF-κB p50 are key co-regulators of IFN-β and IL-6 expression following TLR9-mediated activation of human pDCs. The nuclear accumulation of IRF-1 was also observed, but this was a late event that was dependant on type 1 IFN and unrelated to the initiation of gene expression. IRF-8 was identified as a novel negative regulator of gene activation in CpG-stimulated pDCs. As variants of IRF-5 and IRF-8 were recently found to correlate with susceptibility to certain autoimmune diseases, these findings are relevant to our understanding of the pharmacologic effects of “K” ODN and the role of TLR9 ligation under physiologic, pathologic, and therapeutic conditions.
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DOI：
10.1038/nrrheum.2010.176
发表时间：
2010-12
期刊：
Nature reviews. Rheumatology
影响因子：
--
作者：
通讯作者：
--
影响因子：
5.5
作者：
Jarvinen, Tiina M.;Hellquist, Anna;Kere, Juha
通讯作者：
Kere, Juha
DOI：
10.1084/jem.192.4.595
发表时间：
2000-08-21
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Häcker H;Vabulas RM;Takeuchi O;Hoshino K;Akira S;Wagner H
通讯作者：
Wagner H
影响因子：
20.3
作者：
Li, Peng;Wong, Joyce Jing-Yi;Chin, Keh-Chuang
通讯作者：
Chin, Keh-Chuang
影响因子：
5.5
作者：
Halperin, SA;Dobson, S;Eiden, JJ
通讯作者：
Eiden, JJ