Adaptive Neutrophil Phenotypes and Their Functions in the Maternal Immune Landscape 2674

Abstract Description Successful early pregnancy depends on tightly regulated immune interactions at the feto-maternal interface to support the development of the semi-allogenic fetus. Neutrophils, key components of the innate immune system, play an underexplored role in this context. This study investigates neutrophil abundance, phenotype, function, and interactions in the extravillous trophoblast (EVT) invaded decidua during the first trimester of pregnancy (6–12 weeks gestation). Using high-dimensional flow cytometry and imaging mass cytometry, we identified three distinct neutrophil subsets within the decidua, each displaying unique maturation and activation profiles. Functional analyses revealed that neutrophil activation and degranulation, including granular protein release such as MPO, are critical for modulating the immune microenvironment and promoting EVT invasion. These findings highlight the central role of neutrophils in supporting proper placental development and their potential involvement in pregnancy complications if these processes are disrupted. This work underscores the importance of innate immune mechanisms in maternal-fetal health and early pregnancy success. Funding Sources Supported by FWF DK-MOLIN (W1241); OEAW (Doc Fellowship - 26477); DP-iDP (DOC-31); P35294; FFG-Bridge 1 grant (871284); and the OENB Anniversary Fund (17584) Topic Categories Immune Response Regulation: Cellular Mechanisms (IRC)