Role of maternal-fetal immune tolerance in the establishment and maintenance of pregnancy

Abstract

Normal pregnancy is a contradictory and complicated physiological process. Although the fetus carries the human leukocyte antigen (HLA) inherited from the paternal line, it does not cause maternal immune rejection. As the only exception to immunological principles, maternal-fetal immune tolerance has been a reproductive immunology focus. In early pregnancy, fetal extravillous trophoblast cells (EVTs) invade decidual tissues and come into direct contact with maternal decidual immune cells (DICs) and decidual stromal cells (DSCs) to establish a sophisticated maternal-fetal crosstalk. This study reviews previous research results and focuses on the establishment and maintenance mechanism of maternal-fetal tolerance based on maternal-fetal crosstalk. Insights into maternal-fetal tolerance will not only improve understanding of normal pregnancy but will also contribute to novel therapeutic strategies for recurrent spontaneous abortion, pre-eclampsia, and premature birth.

Figure 1

Maternal–fetal interface cell composition. The placenta provides the interface between the mother and the fetus and mainly includes the myometrium, decidua, maternal spiral artery, villus units, and amnion. The maternal–fetal surface cell composition is complex, comprising embryo-derived EVTs and maternal-derived DSCs and DICs. EVTs mainly carry paternal antigens and participate in placenta formation through proliferation and invasion. DSCs mainly provide nutrients, and DICs secrete cytokines to maintain immune tolerance and defend against infection. The DICs mainly include dNKs, dMs, DCs, uMCs, T cells, and B cells. DCs: Dendritic cells; DICs: Decidual immune cells; dMs: decidual macrophages; dNKs: Decidual natural killer cells; DSCs: Decidual stromal cells; EVTs: Extravillous trophoblast cells; uMCs: Uterine mast cells.

Figure 2

Schematic diagram of maternal–fetal immune tolerance. Immune tolerance starts from paternal antigens carried by sperm coming into contact with the maternal system. The paternal antigens are presented to the DICs by DCs, leading to the proliferation and differentiation of antigen-specific Tregs. The Tregs then migrate to the maternal–fetal interface and reduce dNK cytotoxicity by secreting the anti-inflammatory cytokines TGF-β and IL-10, thereby playing an immune tolerance role and maintaining normal pregnancy. DCs: Dendritic cells; DICs: Decidual immune cells; dNK: Decidual natural killer; IL-10: Interleukin-10; TGF-β: Transforming growth factor beta.