脂联素通过p38 MAPK-STAT5途径调节URSA中Th17/Treg失衡的机制研究

项目名称： 脂联素通过p38 MAPK-STAT5途径调节URSA中Th17/Treg失衡的机制研究

项目编号： No.81501335

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 李维宏

作者单位： 重庆医科大学

项目金额： 18万元

中文摘要： 母胎免疫耐受异常是URSA发生的重要原因，Th17/Treg平衡在母胎免疫应答中发挥重要作用。我们前期发现脂联素可纠正URSA患者外周血中Th17/Treg失衡，其作用可能与p38 MAPK-STAT5通路密切相关，但调控机制不清。本项目拟以URSA患者及模型小鼠为对象，首先明确URSA中Th17/Treg平衡、脂联素信号和p38 MAPK-STAT5通路变化；然后采用重组脂联素治疗URSA小鼠，观察其对模型小鼠Th17/Treg失衡及通路分子的影响；最后磁珠分选获得naive CD4+T细胞体外诱导其向Th17或Treg分化，分别观察在相关基因高表达、低表达或通路阻断时脂联素对Th17/Treg细胞分化、转录调节因子、脂联素受体和信号通路分子表达的影响，旨在明确脂联素调控URSA中Th17/Treg失衡的作用及机制，为阐明脂联素信号、Th17/Treg平衡和URSA之间关系提供实验依据。

中文关键词： 不明原因反复自然流产；脂联素；Th17/Treg；p38；MAPK；STAT5

英文摘要： Abnormal maternal-fetal immune tolerance is the major reason for unexplained recurrent spontaneous abortion (URSA) and Th17/Treg balance plays an important role in maternal-fetal dialogue. Our previous study showed that adiponectin signal protected pregnancy, and its effect may be related with regulating Th17/Treg imbalance of URSA via p38 MAPK-STAT5 pathway. But the regulatory mechanism is unclear. Using URSA patients and mice model, Th17/Treg balance, adiponectin signal and p38 MAPK-STAT5 pathway changes in URSA will be further clarified. Next, URSA model mice will be treated by recombinant adiponectin, and its effects of adiponectin on Th17/Treg imbalance and pathways molecules will be observed. Then, naive CD4+T cells obtained by magnetic bead sorting will be induced toward Th17 or Treg differentiation. The effects of adiponectin on differentiation of Th17/Treg cells, expression of the transcription factor, adiponectin receptors and signaling pathways will be observed in related gene high expression level or low expression level or blocked pathways state. As mentioned above, the role of adiponectin and its downstream MAPK-STAT5 pathway on Th17/Treg will be elucidated in URSA. The results will contribute to elucidating the relationship between adiponectin signaling, Th17/Treg balance and URSA, and then a new theory and target of URSA will be developed.

英文关键词： URSA;adiponectin;Th17/Treg;p38 MAPK;STAT5