57 Fetal Macrophages Produce Interleukin-7 in the Fetal Hematopoietic Niche

Tissue-resident macrophages play critical roles in tissue homeostasis and immunity, and many of them have a distinct fetal origin and developmental trajectory as compared to their adult bone marrow-derived counterparts. However, the specific mechanisms underlying their developmental signaling pathways have not been as thoroughly examined as in the adult. Our lab recently demonstrated that fetal-derived macrophage development is regulated by expression of the lymphoid-associated interleukin-7 receptor (IL-7R) in mice, but the fetal source of the cognate cytokine ligand, interleukin-7 (IL-7), has yet to be determined. This project investigated fetal macrophage cells as a potential source of IL-7 production, with the aim of providing further insight into these signaling pathways during prenatal development. A transgenic mouse model was used that expresses IL-7 attached to green fluorescent protein (GFP) to measure GFP expression as a proxy for IL-7 expression in developing tissues. Embryonic tissues were extracted from mouse fetuses at 17.5 days post-conception and cells were isolated and stained with antibodies to identify blood, endothelial, and fetal macrophage cells as putative sources of IL-7 production. Samples were also intracellularly stained for GFP to quantify the IL-7 production across different cell types within different tissues in the embryo. The resulting data preliminarily identifies fetal macrophages as the primary producers of IL-7 across common tissues in the developing embryo. A better understanding of the developmental signaling pathways that regulate fetal immune development can expand comprehension of the origins of early immune dysfunction and help mitigate disease susceptibility from early life.