Single-cell profiling of the immune landscape at the maternal-fetal interface in unexplained recurrent miscarriage

This study uses single-cell RNA sequencing (scRNA-seq) profiling to explore the heterogeneity of CD4⁺ T cells at the maternal-fetal interface in URM and normal pregnancy groups, and to investigate the cell subsets associated with URM and the underlying pathophysiological mechanisms. Ultimately, it was determined that CD4⁺T cells present at the maternal-fetal interface of URM patients exhibited a significant increase in acute inflammatory response, pro-inflammatory cytokines, and chemokines secreted by macrophages. Additionally, immune plasticity was observed in Treg cells, with a decrease in the expression of CD25, an increase in the constituent ratio of exTreg, and a decrease in the function of Treg to inhibit the inflammation of effector cells. Furthermore, the decrease in Treg receptor CCR4 was found to reduce the ability of Treg migration and local inflammation. The combined presence of PD1^HIIL-10⁺ and TIGIT⁺FOXP3^DIM subtypes in Treg also increased, leading to the inhibition of the decline of CD8⁺ effector cells function. Endothelial cells within the URM group demonstrate elevated levels of CX3CR1, which promote the recruitment of CX3CR1+ cells from the bloodstream and their subsequent migration to tissues. CX3CR1-expressing CD8⁺ T and CD4⁺ T cells undergo differentiation into effector cells equipped with cytotoxic granules, ultimately resulting in vascular and tissue damage. Regulatory T cells play a crucial role in suppressing local inflammation and preserving maternal-fetal immune tolerance. These findings offer a more comprehensive understanding of the dysregulation of the decidual immune microenvironment in URM, potentially informing advancements in the diagnosis and management of this condition.