转录因子E2F1对树突状细胞成熟的抑制作用

发布时间：2018-04-15 11:32

本文选题：E2F1 + 树突状细胞　；参考：《中国科学技术大学》2010年硕士论文

【摘要】： 树突状细胞(Dendritic cell,DC)是目前已知的功能最强的专职抗原提呈细胞(Antigen-presenting cell,APC),可启动并调节免疫应答,有效刺激T、B淋巴细胞活化,在抗肿瘤、抗感染、移植排斥以及自身免疫性疾病发病过程中起重要作用。研究表明,肿瘤患者缺乏有力的抗肿瘤免疫应答,可能原因之一是肿瘤细胞抗原性弱、患者APC功能低下,使肿瘤抗原不能被有效提呈给淋巴细胞。因此通过体外研究树突状细胞成熟过程中起重要作用的基因及其调节机制,然后利用一定的药物恢复肿瘤组织中DC的正常功能,进而激发体内特异性抗肿瘤免疫反应,有可能成为临床抗肿瘤免疫治疗的有效方案。 E2F1传统意义上被认为在细胞周期调控和细胞增殖方面起到调节作用,作为转录因子不仅参与细胞生长调控,也能够在一定程度上诱导凋亡。近来,一些研究发现,E2F1在巨噬细胞应答炎症因子过程中可以调节一大批相关基因的表达,并且在病原体感染情况下可以诱导T细胞的活化。这揭示了E2F1在免疫调节方面有着重要的作用。然而E2F1在DC成熟过程中的作用尚不清楚。在本课题中,我们对人源DC成熟过程中TLRs的表达情况进行了检测,结果显示不同的TLRs在DC的成熟过程中都发生了很大变化;此外我们重点对E2F1对DC的表型和功能的影响进行了研究。结果表明E2F1在人源DC和DC2.4成熟过程中都有暂时性的降低,当E2F1敲低时DC2.4细胞在表型和功能都趋向成熟。相反,E2F1过表达则抑制了LPS对DC2.4的成熟诱导作用。同时发现,敲低E2F1可激活包括Erk1/2, NF-κB和PI3K/Akt在内的DC成熟过程中起重要作用的信号转导通路,提示E2F1参与DC的信号通路的调节。E2F1对DC表型上的成熟抑制作用同时在E2F1敲除鼠骨髓来源的DC上同样得到了证实。上述研究结果提示,E2F1在DC的成熟中起着重要的调节作用。
[Abstract]:Dendritic cell carcinoma (DCD) is the most functional antigen presenting cell (APCP), which can initiate and regulate the immune response, stimulate the activation of TnB lymphocytes, and play an important role in anti-tumor and anti-infection.Transplant rejection and autoimmune disease play an important role in the pathogenesis.It has been shown that one of the possible reasons for the lack of strong anti-tumor immune response in cancer patients is the weak antigenicity of tumor cells and the low function of APC in patients, so that tumor antigens cannot be effectively presented to lymphocytes.Therefore, the important genes and their regulatory mechanisms during dendritic cell maturation were studied in vitro, and then the normal function of DC in tumor tissue was restored by certain drugs, and then the specific anti-tumor immune response was stimulated in vivo.It may be an effective regimen for clinical anti-tumor immunotherapy.E2F1 is traditionally considered to play a regulatory role in cell cycle regulation and cell proliferation. As a transcription factor, it not only participates in the regulation of cell growth, but also induces apoptosis to a certain extent.Recently, some studies have found that E2F1 can regulate the expression of a large number of related genes in macrophage response to inflammatory factors, and can induce the activation of T cells in the case of pathogen infection.This reveals that E2F1 plays an important role in immune regulation.However, the role of E2F1 in DC maturation is unclear.In this paper, we detect the expression of TLRs in the mature process of human DC, and the results show that different TLRs have changed greatly in the process of DC maturation.In addition, we focus on the effects of E2F1 on the phenotype and function of DC.The results showed that E2F1 decreased temporarily during the maturation of human DC and DC2.4, and DC2.4 cells tended to mature in phenotype and function when E2F1 knockout was low.On the contrary, overexpression of E2F1 inhibited the maturation induction of DC2.4 by LPS.It was also found that knockout E2F1 could activate signal transduction pathways that play an important role in DC maturation, including Erk 1 / 2, NF- 魏 B and PI3K/Akt.These results suggest that E2F1 is involved in the regulation of DC signaling pathway. E2F1 inhibits DC phenotypic maturation and is also confirmed on DC derived from bone marrow of E2F1 knockout mice.These results suggest that E2F1 plays an important role in the regulation of DC maturation.
【学位授予单位】：中国科学技术大学
【学位级别】：硕士
【学位授予年份】：2010
【分类号】：R392

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