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

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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Abstract

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.