CCR8 <sup>+</sup> decidual regulatory T cells maintain maternal-fetal immune tolerance during early pregnancy
Z 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
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.