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The human placenta shapes the phenotype of decidual macrophages.

Cell reports (2023-01-15)
Sigrid Vondra, Anna-Lena Höbler, Andreas Ian Lackner, Johanna Raffetseder, Zala Nikita Mihalic, Andrea Vogel, Leila Saleh, Victoria Kunihs, Peter Haslinger, Markus Wahrmann, Heinrich Husslein, Raimund Oberle, Julia Kargl, Sandra Haider, Paulina Latos, Gernot Schabbauer, Martin Knöfler, Jan Ernerudh, Jürgen Pollheimer
ABSTRACT

During human pregnancy, placenta-derived extravillous trophoblasts (EVTs) invade the decidua and communicate with maternal immune cells. The decidua distinguishes into basalis (decB) and parietalis (decP). The latter remains unaffected by EVT invasion. By defining a specific gating strategy, we report the accumulation of macrophages in decB. We describe a decidua basalis-associated macrophage (decBAM) population with a differential transcriptome and secretome compared with decidua parietalis-associated macrophages (decPAMs). decBAMs are CD11chi and efficient inducers of Tregs, proliferate in situ, and secrete high levels of CXCL1, CXCL5, M-CSF, and IL-10. In contrast, decPAMs exert a dendritic cell-like, motile phenotype characterized by induced expression of HLA class II molecules, enhanced phagocytosis, and the ability to activate T cells. Strikingly, EVT-conditioned media convert decPAMs into a decBAM phenotype. These findings assign distinct macrophage phenotypes to decidual areas depending on placentation and further highlight a critical role for EVTs in the induction of decB-associated macrophage polarization.

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