蜕膜CD8+CD122+PD-1+Treg细胞抑制Th17细胞分化及其异常致不明原因复发性流产的机制研究

不明原因复发性流产（URSA）是常见的妊娠相关疾病，母—胎免疫耐受紊乱是其发生的最主要因素。CD8+CD122+PD-1+ T细胞是一类新型CD8+ Treg细胞，具有比传统的CD4+CD25+Foxp3+ Treg细胞更强的免疫调节功能。我们发现：与正常妊娠组相比，孕早期URSA患者蜕膜CD8+CD122+PD-1+ Treg细胞的比例显著降低，而Th17细胞显著升高；蜕膜CD8+CD122+PD-1+ Treg细胞具有分泌IL-10和抑制Naïve CD4+ T细胞向Th17细胞分化的功能。据此，我们推测蜕膜CD8+CD122+PD-1+ Treg细胞能够通过抑制Th17细胞的分化促进母—胎免疫耐受，而其调控异常将导致URSA。本项目将应用经典动物模型和人群临床样本，首次系统研究孕早期蜕膜CD8+CD122+PD-1+ Treg细胞调控Th17细胞分化及其异常致URSA发生的分子机制。

Unexplained recurrent spontaneous abortion (URSA) is a common pregnancy-related disease, and the disruption of maternal-fetal immune tolerance has been considered the most important cause of URSA. As a novel subset of CD8+ regulatory T cells, CD8+CD122+PD-1+ Treg cells are more potent in immune regulation than conventional CD4+CD25+Foxp3+ Treg cells. In our preliminary studies, we found that there is a significant decrease in the percentage of decidual CD8+CD122+PD-1+ Treg cells but an increase in Th17 cells, in the first-trimester URSA patients as compared with normal pregnancies. Furthermore, decidual CD8+CD122+PD-1+ Treg cells are able to secrete amount of IL-10 and inhibit the differentiation of naïve CD4+ T cells into Th17 cells. Therefore, we speculate that decidual CD8+CD122+PD-1+ Treg cells can facilitate maternal-fetal tolerance via the inhibition of Th17-cell differentiation, whereas their abnormal regulation could result in URSA. In this study, we will use the classical animal models and human samples to investigate the molecular mechanisms by which decidual CD8+CD122+PD-1+ Treg cells regulate Th17 cell differentiation and their abnormal regulation causes URSA.