Cutting Edge: Local Proliferation of Uterine Tissue-Resident NK Cells during Decidualization in Mice

Abstract

Natural killer (NK) cells accumulate in adult murine and human uteri during decidualization induced physiologically, pathologically or experimentally. Adoptive transfer studies indicate that uterine NK (uNK) cells arise from circulating progenitors. However, virgin uteri contain few circulating NK1.1+CD49a− conventional NK (cNK) cells while NK1.1+CD49a+ tissue-resident NK (trNK) cells are abundant. Here, we employed a novel, immune competent NK cell-specific reporter mouse to track accumulation of uNK cells during unmanipulated pregnancies. We identified cNK and trNK cells accumulating in both decidua basalis (DB) and myometrium. Only trNK cells showed evidence of proliferation. In parabiosis studies using experimentally-induced deciduomata, the accumulated uNK cells were proliferating trNK cells; migrating NK cells made no contribution. Together, these data suggest proliferating trNK cells are the source of uNK cells during endometrial decidualization.

Uterine Natural Killer Cell Heterogeneity: Lessons From Mouse Models

“…Approximately 70% of lymphocytes at the maternal-fetal interface are uNK cells during early human and mouse gestation; this percentage declines after mid-pregnancy (25). Histologically, uNK cells are localized to human decidua basalis and mouse junctional zone and MLAp (26,27). Notably, they are essentially absent from the mouse placental labyrinth (27).…”

“…Histologically, uNK cells are localized to human decidua basalis and mouse junctional zone and MLAp (26,27). Notably, they are essentially absent from the mouse placental labyrinth (27). Here, "uNK" cells will refer to NK cells in human and mouse implantation sites.…”

“…cNK Cells NK cells are the originating members of an assortment of innate lymphoid cells (ILCs). NK cells are a heterogeneous population in the spleen, circulating blood, and many tissues (27,(32)(33)(34). Historically, most studies investigated conventional NK (cNK) in mouse spleen and human peripheral blood.…”

Tissue-resident memory-like ILCs: innate counterparts of TRM cells

“…Currently, the presence of CD49a + tissue-resident NK cells has been confirmed in multiple organs, such as the skin, uterus, and salivary glands (Sojka et al, 2014;Cortez et al, 2016). Immune cells contribute to the homeostasis of adult uterus, among which tissue-resident NK cells comprise the dominant populations (Fu et al, 2017;Andreotti et al, 2018;Filipovic et al, 2018;Sojka et al, 2018). In mice, more than 60% of the uterine NK subsets express CD49a; in humans, uterine NK cells mostly exhibit CD56 brihgt CD49a + phenotype (Fu et al, 2017).…”

“…In humans, adaptive CD56 bright NKG2C + NK cells are rare in the uterus, while these subsets can be induced by HLA-G and IL-15 during pregnancy (Gamliel et al, 2018). Whether similar NK cell subsets exist in mice has not been explored; nevertheless, pregnancy also induces the expansion and contraction of uterine-resident NK cells in mice and humans (Fu et al, 2017;Filipovic et al, 2018;Sojka et al, 2018).…”