Li Zhuqing, Si Pinxin, Meng Tingting, Zhao Xiaoran, Zhu Chendi, Zhang Dunfang, Meng Shutong, Li Nianyu, Liu Ran, Ni Tianxiang, Yan Junhao, Li Hongchang, Zhao Ning, Zhong Chao, Qin Yingying, Chen WanJun, Chen Zi-Jiang, Jiao Xue
State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Second Hospital, Shandong University, Jinan, Shandong 250012, China.
National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, Shandong 250012, China.
Sci Immunol. 2025 Apr 18;10(106):eado2463. doi: 10.1126/sciimmunol.ado2463.
Regulatory T (T) cells play a vital role in maintaining maternal immune tolerance to the semiallogeneic fetus during pregnancy. T 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 cell subset specifically enriched in the decidua (dT cells). CCR8 dT cells were decreased in patients with recurrent pregnancy loss (RPL) and an abortion-prone mouse model. Depletion of CCR8 dT cells increased susceptibility to fetal loss, with altered decidual immune profiles. Adoptive transfer of CCR8 T 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 cells are required to maintain maternal-fetal tolerance and highlight potential avenues for RPL therapies.
调节性T（Treg）细胞在孕期维持母体对半同种异体胎儿的免疫耐受中发挥着至关重要的作用。人类蜕膜中T细胞群体的异质性和组织特异性功能在很大程度上仍不清楚。在此，我们通过对孕早期蜕膜和孕妇匹配外周血中的人类CD4 T细胞进行单细胞转录组学和T细胞受体测序，鉴定出一种高度活化、具有免疫抑制作用的CCR8 T细胞亚群，该亚群在蜕膜中特异性富集（蜕膜Treg细胞）。复发性流产（RPL）患者和易流产小鼠模型中的CCR8蜕膜Treg细胞减少。CCR8蜕膜Treg细胞的耗竭增加了胎儿丢失的易感性，同时蜕膜免疫谱发生改变。过继转移CCR8 T细胞可挽救易流产小鼠的胎儿丢失。CCR8配体CCL1主要由蜕膜CD49a自然杀伤细胞产生，在RPL患者中显著减少。我们的数据表明，CCR8蜕膜Treg细胞是维持母胎耐受所必需的，并突出了RPL治疗的潜在途径。
