Gestationally dependent immune organization at the maternal-fetal interface

• Published in: Cell reports (Cambridge) 2022-11, Vol.41 (7), p.111651-111651, Article 111651
• Main Authors: Moore, Amber R., Vivanco Gonzalez, Nora, Plummer, Katherine A., Mitchel, Olivia R., Kaur, Harleen, Rivera, Moises, Collica, Brian, Goldston, Mako, Filiz, Ferda, Angelo, Michael, Palmer, Theo D., Bendall, Sean C.
• Format: Article
• Language: English
• Subjects: CyTOF; Female; Fetus; heterogeneity; Humans; mass cytometry; maternal-fetal interface; microenvironment; mononuclear phagocytes; myeloid diversity; neutrophils; PD-L1; Placenta; Pregnancy; tissue specialization
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2022.111651

The immune system and placenta have a dynamic relationship across gestation to accommodate fetal growth and development. High-resolution characterization of this maternal-fetal interface is necessary to better understand the immunology of pregnancy and its complications. We developed a single-cell framework to simultaneously immuno-phenotype circulating, endovascular, and tissue-resident cells at the maternal-fetal interface throughout gestation, discriminating maternal and fetal contributions. Our data reveal distinct immune profiles across the endovascular and tissue compartments with tractable dynamics throughout gestation that respond to a systemic immune challenge in a gestationally dependent manner. We uncover a significant role for the innate immune system where phagocytes and neutrophils drive temporal organization of the placenta through remarkably diverse populations, including PD-L1+ subsets having compartmental and early gestational bias. Our approach and accompanying datasets provide a resource for additional investigations into gestational immunology and evoke a more significant role for the innate immune system in establishing the microenvironment of early pregnancy. [Display omitted] •A framework to assess perturbations of immune homeostasis in pregnancy•Endovascular compartment imparts immune regulation at the maternal-fetal interface•Identification of pregnancy-specific immune network and coordination•Phenotypic specialization of innate cells to placental microenvironments To better understand the immunology of pregnancy, Moore et al. establish a single-cell mass cytometry platform to deeply phenotype immune cells within the maternal-fetal interface. Their analysis highlights a potentially immunoregulatory role for the endovascular compartment of the maternal-fetal interface and localized maternal innate immune specialization throughout gestation.