Human placental villi immune cells help maintain homeostasisin utero

Abstract

Maintenance of healthy pregnancy is reliant on successful balance between the fetal and maternal immune systems. Although maternal mechanisms responsible have been well studied, those used by the fetal immune system remain poorly understood. Using suspension mass cytometry and various imaging modalities, we report a complex immune system within the mid-gestation (17-23 weeks) human placental villi (PV). Further, we identified immunosuppressive signatures in innate immune cells and antigen presenting cells that potentially maintain immune homeostasis in utero. Consistent with recent reports in other fetal organs, T cells with memory phenotypes were detected within the PV tissue and vasculature. Moreover, we determined PV T cells could be activated to upregulate CD69 and proliferate after T cell receptor (TCR) stimulation and when exposed to maternal uterine antigens. Finally, we report that cytokine production by PV T cells is sensitive to TCR stimulation and varies between mid-gestation, preterm (26-35 weeks) and term deliveries (37-40 weeks). Collectively, we elucidated the complexity and functional maturity of fetal immune cells within the PV and highlighted their immunosuppressive potential.

Impaired autophagy with augmented apoptosis in a Th1/Th2-imbalanced placental micromilieu is associated with spontaneous preterm birth

“…Macrophages and T-cells are the major sources of Th1 and Th2 cytokines in the placenta (Houser et al, 2011;Tilburgs et al, 2015). Villous placenta is predominantly populated with placental macrophages (Hofbauer cells) and non-Hofbauer cells, including CD8 + T-lymphocytes, dendritic and natural Frontiers in Molecular Biosciences frontiersin.org killer cells (Pereira, 2018;Pique-Regi et al, 2019;Swieboda et al, 2020;Toothaker et al, 2021). Therefore, the sources of our identified Th1 and Th2 cytokines were predominantly from Hofbauer cells as well as non-Hofbauer villous immune cells (as the maternal blood from the tissue was removed).…”