Regulatory T cells in pregnancy disorders: a multi-dimensional framework for biomarkers and therapeutic strategies.

Pregnancy represents a unique immunological state in which the maternal immune system must maintain tolerance toward the semi-allogeneic fetus while preserving protective immunity against pathogens. Regulatory T cells (Tregs) are central to this balance, coordinating immune suppression, tissue remodeling, and vascular adaptation throughout gestation. Increasing evidence implicates Treg dysregulation in pregnancy disorders, including recurrent pregnancy loss, preeclampsia, and spontaneous preterm labor. Notably, pathological alterations extend beyond changes in cell abundance and involve multi-dimensional defects in suppressive function, lineage stability, spatial distribution, and regulatory signaling. Advances in high-dimensional immune profiling, including single-cell, spatial, and multi-omics approaches have revealed substantial heterogeneity in Treg populations at the maternal-fetal interface and enabled identification of immune signatures with diagnostic and prognostic potential. These insights are reshaping biomarker development from static measurements toward functionally and spatially resolved immune profiling. In this review, we propose a stage-specific and multi-dimensional framework for understanding Treg biology in pregnancy and systematically compare Treg alterations across major pregnancy disorders. We further evaluate the translational potential of circulating and decidual Treg signatures as biomarkers and discuss emerging therapeutic strategies aimed at restoring immune tolerance. Taken together, this framework positions Treg biology as a foundation for biomarker-guided diagnosis and mechanism-based therapeutic interventions in pregnancy complications.