Abstract

Natural killer (NK) cells are members of a rapidly expanding family of innate lymphoid cells (ILCs). While most previously studied NK cells were derived from the mouse spleen and circulate in the blood, recently others and we found tissue-resident NK (trNK) cells in many tissues that resemble group 1 ILCs (ILC1s). During pregnancy, NK cells are the most abundant lymphocytes in the uterus at the maternal-fetal interface and are involved in placental vascular remodeling. Prior studies suggested that these uterine NK (uNK) cells are mostly derived from circulating NK cells. However, the murine virgin uterus contains mostly trNK cells and it has been challenging to determine their contribution to uNK cells in pregnancy as well as other potential function(s) of uNK cells due to the dynamic microenvironment in the pregnant uterus. This review focuses on the origins and functions of the heterogeneous populations of uNK cells during the course of murine pregnancy.

Highlights

  • Uterine Natural Killer CellsWhile most previously studied Natural killer (NK) cells were derived from the mouse spleen and circulate in the blood, recently others and we found tissue-resident NK (trNK) cells in many tissues that resemble group 1 Innate lymphoid cells (ILCs) (ILC1s)

  • Innate lymphoid cells (ILCs) constitute an expanding heterogeneous family of cells that are found resident in tissues [1,2,3,4]

  • A recent re-classification categorized ILCs into five subsets based on transcription factors and cytokine production: ILC1s, ILC2s, ILC3s, lymphoid tissue-inducer (LTi) cells and conventional Natural killer (NK) cells [5, 6]

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Summary

Uterine Natural Killer Cells

While most previously studied NK cells were derived from the mouse spleen and circulate in the blood, recently others and we found tissue-resident NK (trNK) cells in many tissues that resemble group 1 ILCs (ILC1s). Prior studies suggested that these uterine NK (uNK) cells are mostly derived from circulating NK cells. The murine virgin uterus contains mostly trNK cells and it has been challenging to determine their contribution to uNK cells in pregnancy as well as other potential function(s) of uNK cells due to the dynamic microenvironment in the pregnant uterus. This review focuses on the origins and functions of the heterogeneous populations of uNK cells during the course of murine pregnancy. University of Chicago, United States Sumati Rajagopalan, National Institute of Allergy and Infectious Diseases (NIAID),.

INTRODUCTION
Conventional NK Cells
UTERINE ADAPTATION THROUGHOUT GESTATION
NK HETEROGENEITY IN THE UTERUS
ORIGIN OF UNK CELLS
CNK CELL FUNCTION
Placental Vascular Remodeling
Growth Promoting Factors
Memory of Pregnancy
Findings
CONCLUSIONS
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