Transcriptional re-programming of primary macrophages reveals distinct apoptotic and anti-tumoral functions of IRF-3 and IRF-7.
Transcriptional re-programming of primary macrophages reveals distinct apoptotic and anti-tumoral functions of IRF-3 and IRF-7.
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DOI：
10.1002/eji.200838832
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发表时间：
2009-02
影响因子：
5.4
通讯作者：
Hiscott, John
中科院分区：
文献类型：
--
作者：
Goubau, Delphine;Romieu-Mourez, Raphaelle;Solis, Mayra;Hernandez, Eduardo;Mesplede, Thibault;Lin, Rongtuan;Leaman, Douglas;Hiscott, John
免疫调节转录调节因子-干扰素调节因子（IRF）-3和IRF-7具有相似的结构特征，但具有不同的基因调节潜力。例如，腺病毒介导的组成型活性形式的IRF-3的转导在原代人巨噬细胞中引发细胞死亡，而活性IRF-7的表达在体外诱导强的抗肿瘤活性。为了进一步表征参与这些不同细胞应答的靶基因，比较了活性IRF-3或IRF-7转导的原代人巨噬细胞的转录谱，并用于指导进一步的机制研究。促凋亡BH 3唯一蛋白Noxa被鉴定为主要的IRF-3靶基因和IRF-3、双链RNA和水疱性口炎病毒（VSV）诱导的细胞死亡的必需调节剂。还评价了IRF-7和I型IFN产生在增加巨噬细胞免疫刺激能力中的关键作用; IRF-7增加了广泛的干扰素刺激基因的表达，包括免疫调节细胞因子和参与抗原加工和呈递的基因。此外，活性IRF-7增强了巨噬细胞的交叉呈递能力和杀肿瘤活性，并导致体内针对B16黑色素瘤模型的抗肿瘤应答。总之，这些数据进一步突出了IRF-3和IRF-7在编程细胞凋亡、免疫和抗肿瘤应答方面的各自功能。
The immunoregulatory transcriptional modulators - interferon regulatory factor (IRF)-3 and IRF-7 possess similar structural features but distinct gene regulatory potentials. For example, adenovirus mediated transduction of the constitutively active form of IRF-3 triggered cell death in primary human macrophages, whereas expression of active IRF-7 induced a strong anti-tumoral activity in vitro. To further characterize target genes involved in these distinct cellular responses, transcriptional profiles of active IRF-3 or IRF-7 transduced primary human macrophages were compared and used to direct further mechanistic studies. The pro-apoptotic BH3 only protein Noxa was identified as a primary IRF-3 target gene and an essential regulator of IRF-3, double-stranded RNA and vesicular stomatitis virus (VSV) induced cell death. The critical role of IRF-7 and type I IFN production in increasing the immunostimulatory capacity of macrophages was also evaluated; IRF-7 increased the expression of a broad range of interferon-stimulated genes including immunomodulatory cytokines and genes involved in antigen processing and presentation. Furthermore, active IRF-7 augmented the cross-presentation capacity and tumoricidal activity of macrophages and led to an anti-tumor response against the B16 melanoma model in vivo. Altogether, these data further highlight the respective functions of IRF-3 and IRF-7 to program apoptotic, immune, and anti-tumor responses.
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影响因子：
5
作者：
Andersen, J.;VanScoy, S.;Reich, N. C.
通讯作者：
Reich, N. C.
DOI：
10.1084/jem.20050821
发表时间：
2005-09-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Kolumam GA;Thomas S;Thompson LJ;Sprent J;Murali-Krishna K
通讯作者：
Murali-Krishna K
DOI：
10.1084/jem.190.8.1155
发表时间：
1999-10-18
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Fanger NA;Maliszewski CR;Schooley K;Griffith TS
通讯作者：
Griffith TS
影响因子：
5.4
作者：
Grandvaux, N;Servant, MJ;Hiscott, J
通讯作者：
Hiscott, J
影响因子：
56.9
作者：
Blanco, P;Palucka, AK;Banchereau, J
通讯作者：
Banchereau, J