Trends Immunol. 2025 Dec 16:S1471-4906(25)00302-3. doi: 10.1016/j.it.2025.11.006. Online ahead of print.

ABSTRACT

Pregnancy requires dynamic immune adaptations that balance tolerance, homeostasis, and defense at the maternal-fetal interface. Recent advances integrating findings from human placental samples with those from refined animal models now enable a detailed analysis of how cellular responses in mid and late gestation contribute to major obstetrical complications – with distinct clinical manifestations – such as preterm birth, fetal growth restriction, and pre-eclampsia. In this Opinion article we propose a unifying paradigm: the breakdown of maternal-fetal immune homeostasis. We highlight regulatory T cells and decidual macrophages as complementary regulators of antigen-specific tolerance and nonspecific homeostasis, whereas effector T cell infiltration in chronic placental inflammation and neutrophil-driven inflammation in acute chorioamnionitis exemplify pathological immune activation. Together, these examples illustrate how immune programs that sustain mid-to-late pregnancy, when dysregulated, drive pathology and open new therapeutic opportunities.

PMID:41407649 | DOI:10.1016/j.it.2025.11.006