IRF5 and IRF8 modulate the CAL-1 human plasmacytoid dendritic cell line response following TLR9 ligation.
IRF5 and IRF8 modulate the CAL-1 human plasmacytoid dendritic cell line response following TLR9 ligation.
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DOI：
10.1002/eji.201545911
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发表时间：
2016-03
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;Rodriguez LG;Tross D;Tewary P;Bode C;Klinman DM
含有CpG基序的合成寡核苷酸（ODN）刺激人浆细胞样树突状细胞（pDC）产生1型干扰素（IFN）和促炎细胞因子。先前的研究表明，干扰素调节因子（IRFs）在介导CpG诱导的pDC激活中起着核心作用。这项工作探讨了IRF 5和IRF 8（也称为IFN共有序列结合蛋白）对人CAL-1 pDC细胞系中CpG依赖性基因表达的反向作用。该细胞系具有新鲜分离的人pDC的许多表型和功能特性。来自RNA干扰和微阵列研究的结果表明，IRF 5上调TLR 9驱动的基因表达，而IRF 8下调相同的基因。一些发现支持IRF 8通过直接阻断IRF 5的活性来抑制TLR 9依赖性基因表达的结论。首先，IRF 8的抑制活性仅在IRF 5存在时观察到。第二，邻近连接分析显示IRF 8和IRF 5共定位于静息人pDC的细胞质内，并且在CpG刺激后共易位至细胞核。总之，这些发现表明IRF 5和IRF 8，两种具有相反功能的转录因子，控制人pDC中的TLR 9信号传导。
Synthetic oligonucleotides (ODNs) containing CpG motifs stimulate human plasmacytoid dendritic cells (pDCs) to produce type-1 interferons (IFNs) and proinflammatory cytokines. Previous studies demonstrated that interferon regulatory factors (IRFs) play a central role in mediating CpG-induced pDC activation. This work explores the inverse effects of IRF5 and IRF8 (also known as IFN consensus sequence-binding protein) on CpG-dependent gene expression in the human CAL-1 pDC cell line. This cell line shares many of the phenotypic and functional properties of freshly isolated human pDCs. Results from RNA interference and microarray studies indicate that IRF5 upregulates TLR9-driven gene expression whereas IRF8 downregulates the same genes. Several findings support the conclusion that IRF8 inhibits TLR9-dependent gene expression by directly blocking the activity of IRF5. First, the inhibitory activity of IRF8 is only observed when IRF5 is present. Second, proximity ligation analysis shows that IRF8 and IRF5 colocalize within the cytoplasm of resting human pDCs and cotranslocate to the nucleus after CpG stimulation. Taken together, these findings suggest that IRF5 and IRF8, two transcription factors with opposing functions, control TLR9 signaling in human pDCs.
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影响因子：
5.5
作者：
Halperin, Scott A.;Ward, Brian;Martin, J. Tyler
通讯作者：
Martin, J. Tyler
影响因子：
20.3
作者：
Li, Peng;Wong, Joyce Jing-Yi;Chin, Keh-Chuang
通讯作者：
Chin, Keh-Chuang
DOI：
10.1084/jem.20132620
发表时间：
2014-09-22
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Rowland SL;Riggs JM;Gilfillan S;Bugatti M;Vermi W;Kolbeck R;Unanue ER;Sanjuan MA;Colonna M
通讯作者：
Colonna M
影响因子：
20.3
作者：
Ito, T;Kanzler, H;Liu, YJ
通讯作者：
Liu, YJ
影响因子：
5.5
作者：
Klaschik, Sven;Tross, Debra;Klinman, Dennis M.
通讯作者：
Klinman, Dennis M.