Mouse uterine trNKs share phenotypes with human uterine trNKs 3323

Abstract Description Uterine tissue resident natural killer cells (trNKs) are hypothesized to ensure healthy pregnancy by secreting factors that regulate extravillous trophoblast invasion and spiral arterial remodeling in humans. Studies have associated absent or altered trNKs with pregnancy complications. In utero investigation of trNK development and function in pregnancy is limited in human studies. We can utilize mouse models to perform mechanistic and functional studies of trNKs. While mouse pregnancy models have been routinely used to study trNKs, whether mouse trNKs align with human trNKs has yet to be fully defined. We hypothesize that mouse trNK phenotypes overlap with humans. To test this hypothesis, we studied uterine trNKs in pregnant C57BL/6 mice. Mice were sacrificed at gd6.5 when uterine trNKs are most abundant, and uteri were harvested for flow cytometry. We found CD39+ and CD39- trNK subsets that may align phenotypically with human trNKs. CD39+ and CD39- trNKs were 14.0% and 4.5% of total live, CD45+ cells respectively. While CD103+ mouse trNKs were present like in humans, they represented only 0.1% of live, CD45+ cells. These data suggest that mouse uterine trNK subsets have phenotypes that map to human uterine trNKs. Further work is needed to analyze mouse uterine trNK subsets across pregnancy and to elucidate their transcriptomes for comparison to human uterine trNK subsets. Funding Sources Research is supported by NIH/NIAID R01AI177369 and NIGMS T32GM135028-04. Topic Categories Mucosal and Regional Immunology (MUC)