Adaptive Dynamics of the Maternal Immunity in Human Skin During Pregnancy

ongoing

A successful immune adaptation to pregnancy is essential to support mammalian reproductive fitness. Pregnancy presents a immunological dilemma where the maternal immune system must tolerate fetal antigens while maintaining its main protective functions. How the maternal immune system navigates these opposing demands and adapt to pregnancy remains largely unclear. This question is of importance at barrier sites such as the skin that represents a primary portal of infection and inflammatory disorders. Clinical observations support the idea that skin physiology and immunity are altered during pregnancy. Using experimental models, the host laboratory uncovered a remodeling of skin immunity during pregnancy associated with a significant increase in regulatory T cells and an altered dendritic cell network. The goal of our proposal is to understand how pregnancy impacts human skin with the ultimate goal to develop approaches to mitigate inflammatory responses during this critical stage. More specifically, this project aims at exploring how pregnancy impacts human skin immune landscape and putative function both at steady state and in the context of inflammation. This high dimensional analysis will be performed using high resolution transcriptomic technologies including single cell ATAC / RNA sequencing and spatial transcriptomics. My expertise in these approaches will enable me to uncover underlying putative signalling pathways underlying immune cell changes and highlight pregnancy associated altered cell interactions. Candidate pathways will be validated using organoids mimicking pregnant skin. The generated data are expected to capture, for the first time, how the skin adapts to pregnancy. This work may provide fundamental insights into our understanding of maternal immunity and would potentially enable risk prediction and alleviation of inflammatory skin conditions that can appear or be exacerbated in pregnancy.