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S01.2: Regulation of uterine tissue‐resident natural killer cells by reproductive hormones in mice

The human immune system is remarkably variable. Twin studies on peripheral blood immune cells have revealed the combined contribution of heritable and non-heritable (environmental) factors in shaping this diversity. However, degrees and sources of heterogeneity within organ-specific immune compartments, containing tissueresident immune cells, remain largely unknown. Here, differentiation and diversity of uterine natural killer (uNK) cells will be discussed. Employing high-dimensional methods such as advanced flow cytometry, RNAseq, ATACseq, and proteomics, we describe a pathway for continuous human uNK cell differentiation in response to endometrial regeneration and pregnancy. Furthermore, in studies of menstrual blood from monozygotic twins, heritable and non-heritable uNK cell traits couldbe revealed.Altogether, these results highlight factors driving human immune system variation at a local tissue site.