Emerging themes in uterine natural killer cell heterogeneity and function.

Problem Understanding of uterine natural killer (uNK) cell functions during normal pregnancy remains incomplete. Method of study Cloud tag analysis of literature was used to document themes addressed experimentally for uNK cells. Immunohistochemistry, including whole-mount staining of early implantation sites, separation of uNK cells into molecularly distinct subsets, and physiologic measurements in normal and mutant mice, are further advancing understanding of uNK cell biology. Results Literature analyses revealed three key, current uNK cell research themes: angiogenesis, spiral arterial remodeling/pre-eclampsia/hypertension and infertility. UNK cells are being defined as cells potentially regulated by Wnt signaling that are heterogeneous in progenitor source and function and make unique contributions to implantation site development prior to spiral arterial remodeling. Conclusion Future studies are poised to define uNK cell progenitor cells, identify the signaling pathways supporting established uNK cell functions and move current understanding of mouse uNK cells to clinical research questions.