Placenta-Derived Exosomes as a Modulator in Maternal Immune Tolerance During Pregnancy.

Kunfeng Bai,Xintong Li,William S.B Yeung,Jiangming Zhong,Philip C N Chiu,Ernest H Y Ng,Cheuk-Lun Lee

doi:10.3389/fimmu.2021.671093

Abstract

Exosomes are a subset of extracellular vesicles with an average diameter of ~100nm. Exosomes are released by all cells through an endosome-dependent pathway and carry nucleic acids, proteins, lipids, cytokines and metabolites, mirroring the state of the originating cells. The function of exosomes has been implicated in various reproduction processes, such as embryo development, implantation, decidualization and placentation. Placenta-derived exosomes (pEXO) can be detected in the maternal blood as early as 6 weeks after conception and their levels increase with gestational age. Importantly, alternations in the molecular signatures of pEXO are observed in pregnancy-related complications. Thus, these differentially expressed molecules could be the potential biomarkers for diagnosis of the pregnancy-associated diseases. Recent studies have demonstrated that pEXO play a key role in the establishment of maternal immune tolerance, which is critical for a successful pregnancy. To gain a better understanding of the underlying mechanism, we highlighted the advanced studies of pEXO on immune cells in pregnancy.

Highlights

Pregnancy is a complex process associated with numerous biological changes in the maternal body and our understanding of the complicated relationship between the mother and its semi-allograft fetus is still limited [1]
We demonstrated that decidua-derived glycodelin A (GdA) stimulated the conversion of peripheral CD56bright CD16- natural killer (NK) cells to cells with a decidual NK cell-like phenotype via upregulation of CD9, CD49a and production of VEGF [139]
Our understanding of exosome biogenesis and the underlying forces that navigate them to their destination is still lacking

Summary

Introduction

Pregnancy is a complex process associated with numerous biological changes in the maternal body and our understanding of the complicated relationship between the mother and its semi-allograft fetus is still limited [1]. Both exosome-packed B7H6 and sB7H6 are present in the serum of pregnant women (Supplementary Table 1), indicating its potential contribution via a similar mechanism to inhibit NK cells in the establishment of maternal immune tolerance [137]. In addition to reducing the cytotoxicity of NK cells, exosomes from the serum of pregnant women can selectively increase the caspase-3 activity in CD56dim NK cells, pointing to an alternative way of exosome-mediated immune tolerance by inducing apoptosis of the CD56dim NK cells (Supplementary Table 1) [133].

Results

Conclusion