Eomesodermin defines uterine natural killer cells crucial for murine reproductive success — ASN Events

Eomesodermin defines uterine natural killer cells crucial for murine reproductive success (#105)

Josselyn D Barahona 1 , Liping Yang 1 , Wayne Yokoyama 1
  1. Washington University in Saint Louis School of Medicine, Saint Louis, MISSOURI, United States

Uterine natural killer (NK) cells have been thought to be crucial for reproductive success; however, their developmental origins remain elusive. Although the transcription factor, Eomesodermin (Eomes), is known to regulate the development and maturation of conventional NK cells, a role for Eomes as a developmental driver for uterine NK cells has not been previously described. Using flow cytometry analysis, we demonstrate that Eomes is a lineage-determining transcription factor for tissue-resident NK cells in the murine uterus. Loss of Eomes in Ncr1-expressing cells ablated tissue-resident NK cells in both the virgin and pregnant uterus, suggesting that uterine tissue-resident NK cells arise from precursors in the conventional NK cell lineage. Furthermore, we show that the genetic absence of uterine NK cells results in adverse pregnancy outcomes characterized by reduced litter sizes and increased resorption rates. Together, our findings highlight the indispensable role of uterine NK cells in pregnancy and shed light on their lineage determination, identifying Eomes as a key factor in their establishment.