Influence of Maternal Inflammation on Fetal Gamma Delta (γδ) T Cell Development
Winschel, Marlana B Boyson, Jonathan E
Winschel, Marlana B
Boyson, Jonathan E
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Abstract
It's now appreciated that several immune subsets develop during specific developmental windows in the fetus. One example are gd T cells, an unusual tissue-resident T cell subset which play critical roles in infectious disease, tumor surveillance, and autoimmunity. gd T cells are functionally programmed during a critical developmental window in the embryonic thymus. This suggests a disturbance in their development could have long-lasting effects on offspring immunity. Maternal infection during pregnancy has previously been shown to lead to neurodevelopmental disorders and altered offspring immune cell phenotypes. We modeled the effect of maternal inflammation on fetal innate-like gd T cell development using poly I:C and LPS. We found that maternal inflammation resulted in a decrease in fetal thymocyte number and gd T cell number. Additionally, maternal inflammation from poly I:C pushed Vg1 and Vg1-Vg4- gd T cells towards gdT17 programming. These effects were seen at embryonic day 17 until at least neonatal day 6. Using FTOC we saw that IL-6 alone is sufficient to reduce fetal thymocyte number, but does not appear to be responsible for programming of gd T cells towards IL-17 production that was observed in the in vivo models. Taken together, these data suggest that a maternal inflammatory event during fetal development results in fetal thymic involution and altered gd T cell programming towards IL-17 production that lasts until at least neonatal day 6.
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2023-01-01