Expression of the neonatal Fc-receptor in placental-fetal endothelium and in cells of the placental immune system
Terezia Kiskova, Yuliya Mytsko, Martin Schepelmann, Hanns Helmer, Renate Fuchs, Heidi Miedl, Christian Wadsack, Isabella Ellinger
Placenta Volume 78, March 2019, Pages 36-43
The neonatal Fc receptor, FcRn, is expressed in many human tissues, where it serves several functions. In the first place, it extends the serum half-life of its two ligands, IgG and albumin, by protecting them from degradation, mainly in endothelial and hematopoietic cells. In addition, FcRn mediates IgG-based immune responses at mucosal sites. This includes transcytosis of IgG and immune complexes (IC) across epithelial cells, MHC class II-restricted antigen presentation and MHC class I-restricted cross-presentation of IgG-complexed antigens in antigen-presenting cells. FcRn is increasingly exploited in drug delivery applications.
Starting from the second trimester of pregnancy, passive immunity is provided to the human fetus by transplacental transfer of maternal IgG, which depends on the neonatal Fc receptor, FcRn. Over recent years, placental IgG transfer has gained attention for several reasons. Firstly, vaccination of the mother has become an important strategy to increase early life immunity. Secondly, transplacental transport of therapeutic molecules allotted to the fetus is considered a possibility for prenatal disease treatment. Thirdly, microbial antigens and allergens may be transferred across the placenta, most likely as IgG-ICs. Exploiting or influencing placental IgG transport requires a thorough understanding of the underlying cellular transport mechanism.
While FcRn localization in the placental syncytiotrophoblast (STB) has been demonstrated unequivocally, FcRn expression in placental-fetal endothelial cells (pFECs), which are also part of the materno-fetal barrier, remained unclear for many years. Thus, this study aimed to elucidate the spatio-specific expression pattern of FcRn in placental tissue.
FcRn was localized in cytokeratin 7-positive STB and in CD31-positive pFECs in situ. Endothelial expression was confirmed in isolated primary human placental arterial and venous endothelial cells. Additionally, CD68-positive placental macrophages exhibited FcRn expression in situ. Endogenous IgG partially co-localized with FcRn in STB, pFECs, and in placental macrophages.
Placental FcRn expression in endothelial cells and macrophages is analogous to the expression pattern in other organs. FcRn expression in pFECs suggests an involvement of FcRn in IgG transcytosis and/or participation in recycling/salvaging of maternal IgG present in the fetal circulation. FcRn expression in placental macrophages may account for recycling of monomeric IgG and/or processing and presentation of immune complexes.