Influence of Human Papillomavirus E7 Oncoprotein on Maturation and Function of Plasmacytoid Dendritic Cells In Vitro
Influence of Human Papillomavirus E7 Oncoprotein on Maturation and Function of Plasmacytoid Dendritic Cells In Vitro
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人乳头瘤病毒E7癌蛋白对体外浆细胞样树突状细胞成熟和功能的影响
DOI：
10.1007/s12250-018-0069-3
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发表时间：
2018-12-01
影响因子：
5.5
通讯作者：
Cheng, Hao
中科院分区：
文献类型：
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作者：
Han, Rui;Song, Yin-Jing;Cheng, Hao
人乳头瘤病毒（HPV）治疗的主要困难是它的持续性和复发。负载HPV E7癌蛋白的树突状细胞在以前的报告中被评估为细胞疫苗。浆细胞样树突状细胞（Plasmacytoid dendritic cells，pDC）在免疫系统中起着连接先天性免疫应答和适应性免疫应答的重要作用。但它们在HPV E7负载中的功能尚不清楚。为了研究HPV 6 b、11和16型E7蛋白的负载是否影响pDC的活性，用HPV E7蛋白脉冲人外周血分离的pDC和小鼠骨髓来源的pDC。HPV 6 b/11 E7蛋白脉冲后，pDC中CD 40、CD 80、CD 86和MHC II的表达水平显著上调。HPV 6 b/11 E7蛋白对I型IFN和IL-6的分泌和基因表达均有明显的促进作用，且作用强度大于HPV 16 E7蛋白。HPV 6 b/11 E7蛋白脉冲的pDC中TLR信号通路和JNK/p38 MAP激酶信号通路必需因子的表达均增加。提示HPV E7蛋白可促进pDC的分化成熟，激活TLR和MAPK通路，诱导宿主天然免疫应答。pDC负载HPVE 7可能有助于探索新的针对HPV感染的免疫治疗。
The major difficulties of human papillomavirus (HPV) treatment are its persistence and recurrence. The HPV E7 oncoprotein-loaded dendritic cells have been evaluated as cellular vaccine in previous reports. Plasmacytoid dendritic cells (pDCs) play an essential role of connecting the innate immune response and adaptive immune response in the immune system. But they function in HPV E7 loading is unclear. To investigate whether loading of the HPV type 6b, 11, and 16 E7 proteins affects the activity of pDCs, human peripheral blood-separated pDCs and mouse bone marrow-derived pDCs were pulsed with the HPV E7 proteins. The expression levels of CD40, CD80, CD86, and MHC II were significantly upregulated in pDCs upon HPV 6b/11 E7 protein pulse. The secretion and gene expression of type I IFN and IL-6 were both upregulated by HPV 6b/11 E7 proteins, more significant than HPV 16 E7 protein. The expression of essential factors of TLR signaling pathway and JNK/p38 MAP kinase signaling pathway were all increased in HPV 6b/11 E7 proteins pulsed pDCs. Our results suggest that HPV E7 proteins could promote the differentiation and maturation of pDCs and activate the TLR and MAPK pathway to induce host innate immune response. It might be conducive to explore novel immunotherapy targeting HPV infection with HPV E7 loaded pDC.