Early-life immune exposures can profoundly impact lifelong health. A greater understanding of fetal immunity has the potential to help us understand health and disease during gestation, as a neonate, and every stage of life afterward. There are gaps in knowledge regarding cell types that are unique to the fetus, including the nucleated red blood cell. Fascinatingly, unlike adult counterparts, circulating fetal red blood cells are nucleated and possess the capacity to modify gene expression in response to their environment. Red blood cells have classically been disregarded as immunologically inactive due to an inability to respond to external ques. We discovered that fetal nucleated red blood cells are immunologically active and express machinery capable of influencing T-cell fate. Here, we propose to assess the functionality of nucleated red blood cells in facilitating T-cell programming. Our work is poised to describe an unexpected cellular orchestrator of immune programming in utero.
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