Unique Eomes+ NK Cell Subsets Are Present in Uterus and Decidua During Early Pregnancy
Decidual and uterine natural killer (NK) cells have been shown to contribute to the successful pregnancy both in humans and mice. NK cells represent "cytotoxic" group 1 innate lymphoid cells (ILCs) and are distinct from the recently described "helper" ILC1. Here, we show that both in humans and mice the majority of group 1 ILC in endometrium/uterus and decidua express Eomesodermin (Eomes) thus suggesting that they are developmentally related to conventional NK cells. However, they differ from peripheral NK cells. In humans, Eomes+ decidual NK (dNK) cells express CD49a and other markers of tissue residency, including CD103, integrin b7, CD9, and CD69. The expression of CD103 allows the identification of different subsets of IFNg producing Eomes+ NK cells. We show that TGFb can sustain/induce CD103 and CD9 expression in dNK cells and decidual CD34 derived NK cells, indicating that the decidual microenvironment can instruct the phenotype of Eomes+ NK cells. In murine decidua and uterus, Eomes+ cells include CD49a CD49b+ conventional NK cells and CD49a+ cells. Notably, Eomes+CD49a+ cells are absent in spleen and liver. Decidual and uterine Eomes+CD49a+ cells can be dissected in two peculiar cell subsets according to CD49b expression. CD49a+CD49b and CD49a+CD49b+ cells are enriched in immature CD11blowCD27high cells, while CD49a CD49b+ cells contain higher percentages of mature CD11bhighCD27low cells, both in uterus and decidua. Moreover, Eomes+CD49a+CD49b cells decrease during gestation, thus suggesting that this peculiar subset may be required in early pregnancy rather than on later phases. Conversely, a minor Eomes CD49a+ ILC1 population present in decidua and uterus increases during pregnancy. CD49b Eomes+ cells produce mainly TNF, while CD49a CD49b+ conventional NK cells and CD49a+CD49b+ cells produce both IFNg and TNF. Thus, human and murine decidua contains unique subsets of group 1 ILCs, including Eomes+ and Eomes cells, with peculiar phenotypic and functional features. Our study contributes to re examination of the complexity of uterine and decidual ILC subsets in humans and mice and highlights the role of the decidual microenvironment in shaping the features of these cells.
Front. Immunol.