DBA-lectin reactivity defines mouse uterine natural killer cell subsets with biased gene expression

Endometrial decidualization, a process essential for blastocyst implantation in species with hemochorial placentation, is accompanied by an enormous but transient influx of natural killer (NK) cells. Mouse uterine NK (uNK) cell subsets have been defined by diameter and cytoplasmic granule number, reflecting stage of maturity, and by histochemical reactivity with Periodic Acid Schiff (PAS) reagent with or without co-reactivity with Dolichos biflorus agglutinin (DBA) lectin. We asked whether DBA- and DBA+ mouse uNK cells were equivalent using quantitative RT-PCR analyses of flow-separated, midpregnancy (Gestation Day [gd] 10) cells and immunohistochemistry. CD3E (CD3)-IL2RB (CD122)+DBA cells were identified as the dominant Ifng transcript source. Skewed IFNG production by uNK cell subsets was confirmed by analysis of uNK cells from eYFP-tagged IFNG-reporter mice. In contrast, CD3E-IL2RB+DBA+ uNK cells expressed genes compatible with significantly greater potential for IL22 synthesis, angiogenesis, and participation in regulation mediated by the renin-angiotensin system (RAS). CD3E-IL2RB+DBA+ cells were further divided into VEGFA+ and VEGFA- subsets. CD3E-IL2RB+DBA+ uNK cells but not CD3E-IL2RB+DBA- uNK cells arose from circulating, bone marrow-derived progenitor cells by gd6. These findings indicate the heterogeneous nature of mouse uNK cells and suggest that studies using only DBA+ uNK cells will give biased data that does not fully represent the uNK cell population.