Narrative review of the relationship between the maternal-fetal interface immune tolerance and the onset of preeclampsia

Abstract

Background and objective: The establishment of maternal-fetal interface immune tolerance is essential for successful pregnancy. Studies have shown that spontaneous abortion, recurrent abortion, and fetal growth restriction are related to maternal-fetal interface immune dysfunction. Preeclampsia is an idiopathic condition related to pregnancy which manifests as hypertension, proteinuria, and other target organ damage after 20 weeks of gestation. Although the etiology of preeclampsia is still unknown, its pathogenesis is thought to be related to genetics, environment, and metabolism. In recent years, more and more studies have been conducted on the mechanism of immune tolerance at the maternal-fetal interface and the relationship between immune dysregulation and the pathogenesis of preeclampsia. This paper summarizes the latest studies on this topic in order to find new insights into the pathogenesis of preeclampsia and make a reflection on clinical diagnosis and treatment in different phenotype of preeclampsia.

Methods: The research and latest progress published from 2000 to December 2021 on the relationship between maternal-fetal interface immune tolerance and preeclampsia were broadly retrieved and researched using PubMed and Web of Science databases.

Key content and findings: The mechanism of natural killer cells (NK cells) and macrophages at the maternal-fetal interface in immune tolerance, as well as their cytotoxicity and cytokine secretion dysfunction, may be related to the pathogenesis of preeclampsia. The expression of nonclassical type I human leukocyte antigen (HLA) on extravillous trophoblast (EVT) cell were down-regulated in decidua of preeclampsia, which may induce increase EVT death caused by activating of cytotoxic NK cell. In addition, genetic polymorphism of nonclassical type I HLA on the EVT cell membrane may be related to the pathogenesis of preeclampsia, although this is likely to be a combination of 3 nonclassical type I HLA genotypes and requires sequencing to verify.

Conclusions: We demonstrated how the maternal-fetal interface immune dysfunction contribute to the pathogenesis of preeclampsia, further study and clinical trial based on this theory of pathogenesis may reveal new immune treatment method of preeclampsia.

Keywords: Immunity; human leukocyte antigen (HLA); maternal-fetal interface; natural killer cells (NK cells); preeclampsia.