HIV-1的母婴传播（MTCT）率逐年上升，但机制未被阐明。母胎界面的免疫失调被认为是发生HIV-1 MTCT的发病机制之一。母胎界面存在树突状细胞（DC）和自然杀伤（NK）细胞，对维持正常妊娠是必须的。我们发现HIV-1可直接感染作用于间充质干细胞（MSC），并证实MSC可以达到母胎界面处，调节DC和NK。miR-335在HIV-1感染者MSC中表达明显降低。miRNA可调节MSC多种功能。我们推测：低表达miR-335的MSC主要通过FGF8和TGFβ3途径影响母胎界面的DC和NK的免疫应答，导致母胎界面的免疫失衡，诱发MTCT的发生和发展。正常MSC可使HIV-1感染者母胎界面处免疫平衡重建并阻断妊娠中HIV-1 MTCT的发生。本项目将揭示miR-335对MSC的调控机制；阐明MSC调控HIV-1感染者DC和NK细胞及妊娠状态的信号途径，为HIV-1的母婴阻断提供新思路和新方法。

The ratio of HIV-1 mother-to-child transmission (MTCT) is increased by the year, but the mechanism is unknown. The immune unbalance in mater-fetus interface is the one of the important mechanism for HIV-1 MTCT. Natural killer (NK) cell and dendritic cell （DC）are necessary for nomal pregnancy in mater-fetus interface. we have revealed that HIV-1 could infect the mesenchymal stem cell (MSC) directly, moreover, MSC could regulate the functions of DC and NK cells in mater-fetus interface. MicroRNAs are the regulators in MSC, and the expression of miR-335 is decreased in MSC. Therefore, we presume that decreased expression of miR-335 in MSC can result in the immune unbalance of mater-fetus interface via regulating the immuno-responsion of DC and NK cell, miR-335 probably regulate the functions of MSC in mater-fetus interface thruogh the signal approaches of FGF8 and FGFβ3, which can result in the occurrence and development of HIV-1 MTCT. Normal MSC can reconstruct the immune balance in mater-fetus interface and interdict the HIV-1 MTCT in HIV-1 infected mothers. We can reveal the mechanism of miR-335 regulating MSC, the signal approaches of MSC regulating DC and NK cell in mater-fetus interface, which can provide us the new idea and new method in interdiction of HIV-1 MTCT.

HIV-1的母婴传播（MTCT）率逐年上升，但机制未被阐明。母胎界面的免疫失调被认为是发生HIV-1 MTCT的发病机制之一。母胎界面存在树突状细胞（DC）和自然杀伤（NK）细胞，对维持正常妊娠是必须的。我们的研究结果证实MSC细胞株中miR-335表达明显；本研究也已成功地由经过艾滋病母婴阻断治疗并成功分娩的孕妇胎盘蜕膜组织中分离到MSC，并经过传代培养，MSC细胞纯度达到90%以上；构建的pEGFP-C1-miR-335的哺乳动物细胞表达载体可以在母胎界面MSC中高表达miR-335。后续实验中将对高、低表达miR-335对HIV阴性孕妇、HIV阳性未经艾滋病母婴阻断和经母婴阻断孕妇来源的T、DC和NK细胞进行功能性试验，以进一步阐明miR-335对母胎界面MSC的调控，以及这种调控对母胎界面免疫平衡的影响。