PD-1/PD-L1调控蜕膜巨噬细胞在复发性流产中的相关研究
Studies on PD-1/PD-L1 Regulation of Decidual Macrophages in Recurrent Spontaneous Abortion
毛伴云 1张夏兰 2税国鑫 3梅劼 1岳军1
作者信息
- 1. 四川省医学科学院·四川省人民医院 电子科技大学附属医院妇产科,四川 成都 610072
- 2. 四川省妇幼保健院妇科,四川 成都 610045
- 3. 电子科技大学医学院,四川 成都 610054
- 折叠
摘要
目的:探讨程序性死亡受体-1(PD-1)及其配体(PD-L1)对蜕膜巨噬细胞(DMs)分化及胚胎发育的影响.方法:选取2021 年3 月至2024 年1 月就诊于四川省人民医院的复发性流产患者及正常妊娠人工流产患者各20 例,分别作为复发性流产组(RSA组)和正常妊娠组(NP组).取两组患者绒毛组织及蜕膜组织,使用实时荧光定量聚合酶链式反应(qPCR)及蛋白质免疫印迹试验(West-ern bolt)技术检测绒毛组织中PD-L1 mRNA及蛋白的表达情况;使用流式细胞技术检测DMs类型及其PD-1 的表达情况.分组诱导人单核细胞白血病细胞系(THP-1)细胞分化,设立对照组和PD-1 阻断组,加入不同试剂诱导分化,测定不同条件下分化后DMs类型占比.结果:两组患者绒毛组织中均表达PD-L1 蛋白及mRNA,但RSA组中PD-L1 蛋白及mRNA的表达较NP组减少(P<0.05).两组患者蜕膜组织中均有M1 和M2 型巨噬细胞,RSA组中M2 型/M1 型DMs比值较NP组降低(P<0.05),即DMs向M1 型极化;PD-1 在两组表达差异无统计学意义(P>0.05).人THP-1 细胞经过刺激可分化出M1 和M2 型巨噬细胞,PD-1 阻断后,M2 型/M1 型巨噬细胞比值降低(P<0.05),即巨噬细胞向M1 型极化.结论:复发性流产患者中绒毛组织PD-L1 表达下降,DMs向M1 型方向极化;阻断PD-1/PD-L1 通路可使巨噬细胞更多向M1 型方向极化.PD-1/PD-L1 通路对巨噬细胞极化方向的影响可能会给研究RSA的发生机制提供新的思路.
Abstract
Objective:To investigate the impact of programmed death receptor-1(PD-1)and its ligand(PD-L1)on the differentiation of decidual macrophages(DMs)and embryonic development.Methods:20 patients with re-current spontaneous abortion(RSA group)and 20 patients with normal pregnancy induced artificial abortion(NP group)were selected from Sichuan Provincial People's Hospital between March 2021 and January 2024.Villous and decidual tissues were obtained from both groups.Real-time fluorescent quantitative polymerase chain reac-tion(qPCR)and Western blot techniques were used to detect the expression of PD-L1 mRNA and protein in vil-lous tissues.Flow cytometry was used to analyze the types of DMs and their PD-1 expression.Human monocytic leukemia cells(THP-1)were differentiated under different conditions,with a control group and a PD-1 blocked group established,and different reagents were added into those two groups to induce differentiation,then the pro-portion of DMs types was measured in both groups.Results:PD-L1 protein and mRNA were expressed in the vil-lous tissue of both groups of patients but the expression of PD-L1 protein and mRNA was reduced in the RSA group compared to the NP group(P<0.05).The decidual tissues of both groups contained M1 and M2 macro-phages.Compared with the NP group,the ratio of M2 to M1 DMs in the RSA group was lower(P<0.05),indica-ting a polarization towards the M1 type in DMs.There was no statistically significant difference in PD-1 expression between the two groups(P>0.05).Human THP-1 cells can be stimulated to differentiate into M1 and M2 macro-phages.Afterblocking PD-1,theratioof M2 to M1 macrophages decreased(P<0.05),indicating a polarization towards the M1 type in macrophages.Conclusions:In patients with RSA,the expression of PD-L1 in villous tis-sues is decreased,and DMs polarize towards the M1 type.Blocking the PD-1/PD-L1 pathway can further promote the polarization of macrophages towards the M1 type.The influence of PD-1/PD-L1 pathway on macrophage po-larization may provide new insights into the pathogenesis of RSA.
关键词
程序性死亡受体-1/程序性死亡受体-1配体/蜕膜巨噬细胞/复发性流产Key words
Programmed death receptor-1/Programmed death receptor-1 ligand/Decidual macrophages/Re-current spontaneous abortion引用本文复制引用
基金项目
四川省科技厅重点研发项目(2021YFS0209)
出版年
2024
国家科技期刊平台
NSTL
万方数据