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正常妊娠(NP)供体和复发性妊娠丢失(RPL)患者外周血和胎盘中 γδ T 细胞的综合 RNA 表达谱分析。

Comprehensive RNA expression profile analysis of γδ T cells from peripheral blood and decidual tissues in normal pregnancy (NP) donors and patients with recurrent pregnancy loss (RPL).

机构信息

Department of Obstetrics and Gynecology, The First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi 341000, China.

Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China.

出版信息

J Leukoc Biol. 2023 Mar 1;113(3):334-347. doi: 10.1093/jleuko/qiad009.

Abstract

Recurrent pregnancy loss (RPL) is a significant adverse pregnancy complication. The loss of immune tolerance has been proposed in the pathogenesis of RPL, however, the role of γδ T cells in RPL is still controversial. In this study, the gene expression patterns of circulated and decidual tissue-resident γδ T cells from normal pregnancy donors and patients with RPL were analyzed by SMART-seq. We demonstrate that the transcriptional expression profile of different subsets of γδ T cells in peripheral blood and decidual tissue is strikingly different. Vδ2 γδ T cells, as the major cytotoxic subset, are found to be enriched considerably, and the potential cytotoxicity of this subset is further enhanced in the decidua of RPL patients may be due to detrimental ROS reduction, enhanced metabolic activity, downregulation of immunosuppressive molecules expression in resident γδ T cells. Time-series Expression Miner (STEM) analysis of transcriptome indicates complex changes in gene expression in decidual γδ T cells over time from NP and RPL patients. Taken together, our work identifies high heterogeneity of gene signature in γδ T cells from NP and RPL patients between peripheral blood and decidua, which will be a useful resource for further studies of the critical roles of γδ T cells in RPL.

摘要

复发性流产(RPL)是一种严重的不良妊娠并发症。免疫耐受的丧失被认为是 RPL 的发病机制之一,但 γδ T 细胞在 RPL 中的作用仍存在争议。在这项研究中,我们通过 SMART-seq 分析了正常妊娠供体和 RPL 患者循环和蜕膜组织驻留 γδ T 细胞的基因表达模式。我们证明了外周血和蜕膜组织中不同 γδ T 细胞亚群的转录表达谱明显不同。Vδ2 γδ T 细胞作为主要的细胞毒性亚群,在 RPL 患者的蜕膜中被大量富集,并且该亚群的潜在细胞毒性可能归因于有害 ROS 减少、代谢活性增强、驻留 γδ T 细胞中免疫抑制分子表达下调。对来自 NP 和 RPL 患者的蜕膜 γδ T 细胞转录组的时间序列表达 Miner(STEM)分析表明,随着时间的推移,基因表达发生了复杂的变化。总之,我们的工作确定了 NP 和 RPL 患者外周血和蜕膜中 γδ T 细胞的基因特征存在高度异质性,这将为进一步研究 γδ T 细胞在 RPL 中的关键作用提供有用的资源。

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