中国免疫学杂志2025,Vol.41Issue(10):2305-2312,8.DOI:10.3969/j.issn.1000-484X.2025.10.001
Kisspeptin通过调节母胎界面Treg细胞亚群参与复发性流产的发生
Kisspeptin modulates Treg cell subsets at maternal-fetal interface in recurrent spontaneous abortion
摘要
Abstract
Objective:To investigate whether kisspeptin can influence the maternal-fetal interface regulatory T cells(Treg),thereby participating in the pathogenesis of recurrent spontaneous abortion(RSA).Methods:Normal pregnancy(NP)and RSA mice models were established,where NP mice received a tail vein injection of PBS(NP-PBS group),and RSA mice received a tail vein in-jection of PBS(RSA-PBS group)and active fragment of kisspeptin KP10(RSA-KP10 group),observing embryo absorption rates.Im-munohistochemistry was employed to assess expressions of kisspeptin and Foxp3 in mice uterine tissues.Peripheral blood Treg cells were isolated and expanded through magnetic bead separation.Intervention with KP10 and KP234(kisspeptin receptor antagonist)was administered,and flow cytometry was used to detect levels of IL-10 and TGF-β1 secretion by Treg cells,as well as differences in proliferation and apoptosis.RNA-Seq transcriptomic sequencing was conducted on uterine tissues from RSA-PBS group and RSA-KP10 group of mice.Differentially expressed genes(DEGs)were subjected to GO,KEGG and GSEA enrichment analyses.Results:Embryo absorption rate in RSA mice was higher than that in NP mice,the embryo absorption rate was decreased after tail vein injec-tion of KP10.Expressions of kisspeptin and Foxp3 in uterus of RSA mice was lower than that in NP mice,while increased after injec-tion of KP10.Kisspeptin could modulate the secretion of IL-10 and TGF-β1 by Treg cells,influencing their proliferation without affect-ing apoptosis.Enrichment analysis results showed that DEGs were mainly enriched in reproductive structure development,IL-17,and TGF-β signaling pathways.Conclusion:Kisspeptin can influence both the quantity and function of Treg cells,offering a new theoreti-cal foundation for investigating the pathogenesis and treatment of RSA.关键词
Kisspeptin/复发性流产/Treg细胞/转录组学测序Key words
Kisspeptin/Recurrent spontaneous abortion/Treg cells/RNA-Seq分类
医药卫生引用本文复制引用
杨艳红,宋赛哲,丁思思,杨丽,刘翠平,张弘..Kisspeptin通过调节母胎界面Treg细胞亚群参与复发性流产的发生[J].中国免疫学杂志,2025,41(10):2305-2312,8.基金项目
国家自然科学基金面上项目(81873835,82071726) (81873835,82071726)
苏州市科技计划项目(SKY2022005,SKY2023138) (SKY2022005,SKY2023138)
苏州市姑苏卫生人才计划培养项目(GSWS2020011). (GSWS2020011)