艾滋病患者淋巴滤泡中CXCR5+NK细胞介导的抗病毒免疫应答及其作用机制研究

淋巴结是HIV复制和潜伏的主要位置，NK细胞在抗病毒感染中发挥重要作用，但淋巴结NK细胞介导的抗病毒免疫应答在抗HIV感染中的作用尚不清楚。我们前期研究结果发现，淋巴结中CXCR5+NK细胞主要定位于淋巴滤泡区域，与CXCR5-NK细胞相比具有更强的抗病毒感染的潜能；HIV感染引起淋巴结CXCR5+NK细胞比例升高，且CXCR5+NK细胞的比例与HIV-DNA呈负相关。然而，CXCR5+NK细胞迁移进入淋巴滤泡区域并发挥抗病毒作用的机制需进一步研究，CXCR5+NK细胞的关键转录调控网络需进一步明确。本课题拟采用流式细胞术、多重荧光免疫组化、单细胞测序等技术，利用HIV患者淋巴结和外周血样本，阐明淋巴结CXCR5+NK细胞介导的免疫应答在慢性HIV感染中的作用以及调控CXCR5+NK细胞的关键分子机制，为艾滋病功能性治愈提供新的靶点，为下一步临床应用提供理论依据。

Lymph nodes constitute the major location for HIV replication and reservoir. Although NK cells play an essential role in anti-HIV infection, the immune responses of NK cells in lymph nodes are poorly understood. Our previous studies have shown that CXCR5+NK cells are mainly located in lymphoid follicles and display stronger anti-viral potentials than CXCR5-NK cells. In addition, the frequencies of CXCR5+NK cells are increased during HIV infection and show negative correlation with HIV-DNA in lymph nodes. However, further research is still needed to investigate the mechanisms of the migration of CXCR5+NK cells into lymphoid follicles and the antiviral effect mediated by CXCR5+NK cells. Besides, the key transcription factors and regulatory network governing CXCR5 expression in NK cells still need to be clarified. Technologies such as flow cytometry, fluorescent multiplex immunohistochemistry and single cell sequencing will be applied in our study. Lymph node and peripheral blood samples will be employed to study the role of CXCR5+NK cell-mediated immune responses and the key molecular mechanisms regulating CXCR5 expression in NK cells during chronic HIV infection. This study might reveal new targets for functional cure of HIV and provide theoretical basis for further clinical application.