CCR8 +个体调节性T细胞在妊娠早期维持母胎免疫耐受

IF 17.6 1区医学 Q1 IMMUNOLOGY

Science Immunology Pub Date : 2025-04-18 DOI:10.1126/sciimmunol.ado2463

Zhuqing Li, Pinxin Si, Tingting Meng, Xiaoran Zhao, Chendi Zhu, Dunfang Zhang, Shutong Meng, Nianyu Li, Ran Liu, Tianxiang Ni, Junhao Yan, Hongchang Li, Ning Zhao, Chao Zhong, Yingying Qin, WanJun Chen, Zi-Jiang Chen, Xue Jiao

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引用次数: 0

摘要

在怀孕期间，调节性T细胞在维持母体对半异体胎儿的免疫耐受中起着至关重要的作用。人类蜕膜中的T细胞群异质性和组织特异性功能在很大程度上仍然未知。在这里，我们利用来自妊娠早期蜕膜和匹配的孕妇外周血的CD4 + T细胞的单细胞转录组学和T细胞受体测序，发现了一个高度激活的、免疫抑制的CCR8 + T regg细胞亚群（dT regg细胞）在蜕膜中特异性富集。在复发性妊娠丢失（RPL）患者和流产倾向小鼠模型中，CCR8 + dT regg细胞减少。CCR8 + dT regg细胞的缺失增加了胎儿丢失的易感性，并改变了个体免疫谱。CCR8 + T细胞过继移植可挽救易流产小鼠胎儿丢失。CCR8配体CCL1主要由蜕膜CD49a +自然杀伤细胞产生，在RPL患者中显著降低。我们的数据表明，CCR8 + dT regg细胞是维持母胎耐受性所必需的，并强调了RPL治疗的潜在途径。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

CCR8+ decidual regulatory T cells maintain maternal-fetal immune tolerance during early pregnancy

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CCR8+ decidual regulatory T cells maintain maternal-fetal immune tolerance during early pregnancy

Regulatory T (T_reg) cells play a vital role in maintaining maternal immune tolerance to the semiallogeneic fetus during pregnancy. T_reg cell population heterogeneity and tissue-specific functions in the human decidua remain largely unknown. Here, using single-cell transcriptomic and T cell receptor sequencing of human CD4⁺ T cells from first-trimester deciduae and matched peripheral blood of pregnant women, we identified a highly activated, immunosuppressive CCR8⁺ T_reg cell subset specifically enriched in the decidua (dT_reg cells). CCR8⁺ dT_reg cells were decreased in patients with recurrent pregnancy loss (RPL) and an abortion-prone mouse model. Depletion of CCR8⁺ dT_reg cells increased susceptibility to fetal loss, with altered decidual immune profiles. Adoptive transfer of CCR8⁺ T_reg cells rescued fetal loss in abortion-prone mice. The CCR8 ligand CCL1 was mainly produced by decidual CD49a⁺ natural killer cells and was significantly decreased in patients with RPL. Our data demonstrate that CCR8⁺ dT_reg cells are required to maintain maternal-fetal tolerance and highlight potential avenues for RPL therapies.

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来源期刊

Science Immunology Immunology and Microbiology-Immunology

CiteScore

32.90

自引率

2.00%

发文量

183

期刊介绍： Science Immunology is a peer-reviewed journal that publishes original research articles in the field of immunology. The journal encourages the submission of research findings from all areas of immunology, including studies on innate and adaptive immunity, immune cell development and differentiation, immunogenomics, systems immunology, structural immunology, antigen presentation, immunometabolism, and mucosal immunology. Additionally, the journal covers research on immune contributions to health and disease, such as host defense, inflammation, cancer immunology, autoimmunity, allergy, transplantation, and immunodeficiency. Science Immunology maintains the same high-quality standard as other journals in the Science family and aims to facilitate understanding of the immune system by showcasing innovative advances in immunology research from all organisms and model systems, including humans.