Research ArticleNK CELLS

Continuous human uterine NK cell differentiation in response to endometrial regeneration and pregnancy

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Science Immunology  19 Feb 2021:
Vol. 6, Issue 56, eabb7800
DOI: 10.1126/sciimmunol.abb7800

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NK cells ride the uterine cycle

Tissue-resident natural killer (NK) cells in the uterus promote successful pregnancies by regulating the depth of placental trophoblast invasion. Endometrial tissue is naturally subject to constant remodeling in response to hormonal fluctuations during the menstrual cycle, but how the changing uterine microenvironment influences the heterogeneity of uterine NK (uNK) cells is poorly understood. Strunz et al. used proteomic and transcriptomic techniques to profile human uNK cells recovered from different stages of the menstrual cycle and during pregnancy. This analysis identified sequentially expressed uNK cell surface markers that define a recurring cycle of differentiation in response to progesterone-regulated release of stromal IL-15. These findings pave the way for further studies on how uNK cell functions are modulated by the dynamic endometrial microenvironment.

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