Eomesodermin defines uterine NK cells crucial for pregnancy success in mice

Abstract

Uterine natural killer cells have been thought to be critical for reproductive success, and their developmental origins remain unclear. Here, we demonstrate that Eomesodermin is a key transcription factor determining the lineage of tissue-resident NK cells within the uterus both at steady-state and during pregnancy. Ablation of Eomesodermin in Ncr1-expressing cells results in the loss of tissue-resident NK cells in both the virgin and pregnant uterus, suggesting that uterine tissue-resident NK cells derive from precursors in the conventional NK cell lineage. We further show that the genetic absence of uterine NK cells during murine gestation leads to adverse pregnancy outcomes marked by reduced litter sizes and increased resorption rates. Collectively, our data underscore the pivotal role of uNK cells in pregnancy and offer novel insights into their lineage specification, revealing Eomesodermin as a crucial factor in their establishment.