以CD5为核心的HPV相关宫颈疾病发生发展的免疫学预测、诊治靶标探索

人乳头瘤病毒（HPV）相关宫颈疾病严重危害妇女健康，而HPV高感染率（80%）和感染后相关宫颈疾病偶发生率(4%)提示：HPV与宿主免疫间的复杂相互作用对HPV感染后宫颈病变发生发展至关重要。我们前期HPV相关宫颈疾病易感性和免疫防治研究的大量实验证据揭示：基于宫颈疾病发生发展中核心因素的检测分析对疾病早期诊治、疗效观察、预后评估有极大现实意义。本项目从我们已初步证实的HPV感染后不同宫颈疾病免疫微环境中CD5+T细胞有明显差异出发，深入挖掘HPV感染与宿主免疫的复杂关系，依托组织细胞3D培养模型及腺相关病毒携带siRNA构建的CD5基因敲除小鼠模型，并利用Rag2基因敲除的CD5+T细胞输注动物模型，探索CD5在HPV感染后不同宫颈疾病发生发展的作用特征，并结合临床数据采用数学建模等方法，以期筛选验证敏感特异的HPV感染后宫颈疾病发生发展预测指标，为制定精准的HPV感染诊疗策略提供支持。

Human papillomavirus (HPV) related cervical diseases is severely impaired women’s health, however, the high HPV infection rate (80%) across the whole population and occasional post-infectious occurrence of cervical diseases(CD)(4%) hint that there is a complicated relationship between HPV-host-immunity. Our previous research about the susceptibility for HPV related CD and immune prevention and treatment of CD proved that the cooperation of the host and carcinogenic factor had core function on the HPV persistent infection and integration. This project will base on the research about the change of immune microenvironment which had a significant different at CD5+T cells level with different CD states, and regarding CD5 as a clue, deeply exploring the changes of immune microenviroment after HPV infection. Depending on the tissue cell 3D culture model in vitro and the adeno-associated virus carry the SiRNA sequence constructing the CD5 knock-out mice model and re-transport CD5+T cell to Rag2 knock-out mice model in vivo, clarify the different characters of immune factors after HPV infection. Meanwhile, taking together of the experiment results and the clinic data into account, employ math model to select the sensitive and distinctive markers of CD prognosis and support establishment the accurate HPV infection diagnosis and treatment strategy.