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

Regulatory T cells (Tregs) play crucial roles in maintaining maternal immune tolerance to the semi-allogeneic fetus during pregnancy, but Treg population heterogeneity and tissue-specific functions in human decidua remain largely unknown. Here, we conducted single-cell transcriptomic and T cell receptor sequencing of CD4+ T cells from first-trimester decidua and matched peripheral blood of pregnant women. These analyses identified a highly activated, immunosuppressive CCR8+ Treg subset specifically enriched in decidua (dTregs). CCR8+ dTregs are decreased in recurrent pregnancy loss (RPL) patients and abortion-prone model mice. Depletion of this subset with anti-CCR8 antibodies alters the decidual immune profile, increasing susceptibility to fetal loss. The CCR8 ligand, CCL1, is mainly produced by decidual CD49a+ NK cells and is also significantly decreased in RPL patients. By characterizing the landscape of dTregs in human early pregnancy, we identified CCR8+ dTregs as crucial for maintaining maternal-fetal tolerance, suggesting new potential strategies for RPL diagnosis and therapy.