促红细胞生成素通过JAK2/STAT3信号通路上调细胞程序性死亡-配体1稳定Th17/Tregs比例促进母胎耐受的机制研究

感染是早产的一个重要因素。感染性早产与辅助性T细胞17（Th17）/调节性T细胞（Tregs）比例失衡引起的母胎不耐受有关。我们发现感染性早产患者胎盘滋养细胞中细胞程序性死亡-配体1（PD-L1）与足月胎儿比较低表达，且在感染性早产动物中促红细胞生成素（EPO）能显著抑制早产；EPO可上调小鼠胎盘滋养细胞PD-L1及磷酸化信号传导及转录激活蛋白3（p-STAT3）的表达。EPO通过JAK2/STAT3信号通路上调胎盘滋养细胞PD-L1蛋白的表达，稳定外周及母胎界面Th17/Tregs比例，抑制感染性早产仍鲜见报道。本项目拟在明确EPO抑制感染性早产，并提高胎儿的存活率作用的基础上，采用基因工程小鼠、激酶抑制剂等工具，从正向和反向在细胞、动物和人群三个水平探讨EPO抑制感染性早产的机制，为有效开发抑制早产的新治疗药物提供科学依据.

Infection is an important factor leading to preterm birth.The infection-induced preterm birth is associated with feto-maternal intolerance caused by an imbalance in the ratio of T helper cell 17(Th17)/regulatory cells(Tregs).We have found that the programmed cell death-ligand 1 (PD-L1) expression in the placental trophoblast cells of patients with infection-induced preterm birth was lower than that of the women with full-term birth and erythropoietin(EPO) significantly prevented preterm labor in an infection induced preterm delivery model, and EPO increased the expressions of PD-L1 and p-STAT3 in LPS-treated mice.It is rarely reported that EPO up-regulates the expression of PD-L1 in placental trophoblast cells through the JAK2/STAT3 signaling pathway to stabilizes the ratio of Th17/Tregs in the periphery and locally at the feto-maternal interface, and inhibits infection-induce preterm birth.This project clarified the role of EPO in inhibiting infection-induced preterm birth and increasing fetal survivals and on this basis,we intends to use the genetically engineered mice, kinase inhibitors and other tools to explore the mechanism of EPO preventing infection-induced preterm birth at the cells,animals and population levels,which will provide a scientific basis for exploring new drugs of effectively preventing preterm birth.