Work

The maternal-fetal interface as an immunological barrier: Structure, regulation, and breakdown

Year: 2026

Type: article

Abstract: The maternal-fetal interface is a specialized immunological barrier composed of the decidua, the intervillous space, and the fetal membranes, each forming distinct sites of the maternal-fetal interaction. Across gestation, these compartments coordinate tolerance to the semi-allogeneic fetus, antimicrobial defense, and the inflammatory signaling required for labor. This review integrates human and murine studies to describe how immune populations function within this barrier. Early gestation depends on macrophages, regulatory T cells, and uterine natural killer cells to support implantation and vascular remodeling. Mid- and late gestation feature sustained Treg activity, homeostatic macrophages, Hofbauer cells, and reduced, tolerogenic dendritic cells that together maintain immune quiescence. Near term, a programmed shift toward inflammation facilitates parturition, with exhausted decidual T cells acting as restrained modulators. Finally, we discuss chronic placental inflammation as a breach of the maternal-fetal barrier, characterized by maternal T cell infiltration into fetal tissues and acquisition of cytotoxic effector phenotypes.

Source: Cell Reports

DOI: 10.1016/j.celrep.2026.117164

Authors: Eva Kareus, Dustyn Levenson, Seungbaek Lee, Nardhy Gomez-Lopez

Institutions: Washington University in St. Louis, Wayne State University

Language: English

Topic: Reproductive System and Pregnancy

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $5,620