Visualizing Dynamic Changes at the Maternal-Fetal Interface Throughout Human Pregnancy by Mass Cytometry
Anita van der Zwan (Leiden University Medical Center)
Vincent van Unen (Leiden University Medical Center, Stanford University School of Medicine)
Guillaume Beyrend (Leiden University Medical Center)
Sandra Laban (Leiden University Medical Center)
Carin van der Keur (Leiden University Medical Center)
Hanneke J.M. Kapsenberg (Leiden University Medical Center)
Thomas Höllt (Leiden University Medical Center, TU Delft - Electrical Engineering, Mathematics and Computer Science)
Susana M. Chuva de Sousa Lopes (Leiden University Medical Center)
Marie-Louise P. van der Hoorn (Leiden University Medical Center)
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Abstract
During healthy pregnancy, a balanced microenvironment at the maternal-fetal interface with coordinated interaction between various immune cells is necessary to maintain immunological tolerance. While specific decidual immune cell subsets have been investigated, a system-wide unbiased approach is lacking. Here, mass cytometry was applied for data-driven, in-depth immune profiling of the total leukocyte population isolated from first, second, and third trimester decidua, as well as maternal peripheral blood at time of delivery. The maternal-fetal interface showed a unique composition of immune cells, different from peripheral blood, with significant differences between early and term pregnancy samples. Profiling revealed substantial heterogeneity in the decidual lymphoid and myeloid cell lineages that shape gestational-specific immune networks and putative differentiation trajectories over time during gestation. Uncovering the overall complexity at the maternal-fetal interface throughout pregnancy resulted in a human atlas that may serve as a foundation upon which comprehension of the immune microenvironment and alterations thereof in pregnancy complications can be built.