Sgarbanti Marco, Marsili Giulia, Remoli Anna Lisa, Orsatti Roberto, Battistini Angela
Department of Infectious, Parasitic and Immunomediated Diseases, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
Ann N Y Acad Sci. 2007 Jan;1095:325-33. doi: 10.1196/annals.1397.036.
The interferon regulatory factor 7 (IRF-7), a member of the IRF family of transcription factors, is a key player in the innate immune response against viral infections. Constitutive expression of IRF-7 is limited to peripheral blood lymphocytes and dendritic cells while in most cell types its expression can be induced by type I interferon (INF). IRF-7 is sequestered in the cytoplasm of uninfected cells and following viral infection, double-stranded RNA (dsRNA), or toll-like receptor (TLR) signaling, it becomes phosphorylated by TBK and IKK-i kinases. Phosphorylated IRF-7 migrates in the nucleus where it can activate IFN type I genes and other interferon-stimulated genes (ISGs). Here we report that the overexpression of a constitutively active form of IRF-7 binds and positively regulates the transcriptional activity of the promotor of IRF-1 and low molecular mass polypeptide-2 (LMP-2), two proteins that play a key role in adaptive immunity. The so far unrecognized role of IRF-7 in LMP-2 stimulation points to IRF-7 as a transcriptional regulator that bridges innate and adaptive immunity.
干扰素调节因子7(IRF-7)是转录因子IRF家族的成员,是针对病毒感染的先天免疫反应中的关键因子。IRF-7的组成型表达仅限于外周血淋巴细胞和树突状细胞,而在大多数细胞类型中,其表达可由I型干扰素(INF)诱导。IRF-7在未感染细胞的细胞质中被隔离,在病毒感染、双链RNA(dsRNA)或Toll样受体(TLR)信号传导后,它被TBK和IKK-i激酶磷酸化。磷酸化的IRF-7迁移到细胞核中,在那里它可以激活I型干扰素基因和其他干扰素刺激基因(ISG)。在这里,我们报告说,组成型活性形式的IRF-7的过表达结合并正向调节IRF-1和低分子量多肽-2(LMP-2)启动子的转录活性,这两种蛋白质在适应性免疫中起关键作用。IRF-7在LMP-2刺激中迄今未被认识的作用表明,IRF-7是一种连接先天免疫和适应性免疫的转录调节因子。