CD56brightCD25+ NK cells are preferentially recruited to the maternal/fetal interface in early human pregnancy

Abstract

Decidual natural killer (dNK) cells are believed to be critical for maintaining maternal/fetal tolerance and regulating placental vascular remodeling based upon their abundance and unique phenotype during early pregnancy. However, the mechanism for how the dNK cells play such important roles in successful pregnancy remains undefined. Here, we identified a subtype of dNK cells characterized as having a CD3 2 CD56 bright CD25 1 phenotype. We found that CD56 bright CD25 1 NK cells preferentially localize to the maternal/fetal interface during early human pregnancy. CD25 1 dNK cells account for approximately 75% of CD25-expressing decidual immune cells (DICs). However, less than 5% of CD25-positive peripheral blood mononuclear cells are CD25 1 NK cells. Furthermore, CD25 1 and CD25 2 dNK cells exhibit distinct phenotypes: CD25 1 dNK cells display a more activated phenotype and greater cytokine-secreting capacity. Interestingly, coculture of peripheral NK (pNK) cells with primary trophoblasts upregulates the percentage of CD25-expressing pNK cells, resulting in increased expression of activation markers and cytokine production by pNK cells. In addition, we demonstrated that the CXCL12/CXCR4 axis is crucial for the recruitment of CD25 1 dNK cells and contributes to the accumulation of CD3 2 CD56 bright CD25 1 dNK cells at the maternal/fetal interface. Thus, our data reveal that the crosstalk between trophoblasts and pNK cells leads to the accumulation of CD3 2 CD56 bright CD25 1 dNK cells, which exert a regulating effect at the maternal/fetal interface.

The Galectin-9/Tim-3 pathway is involved in the regulation of NK cell function at the maternal–fetal interface in early pregnancy

“…15,36 The environment at the maternal-fetal interface is assumed to modify recruited pNK cells, instructing them to be dNK-like cells in phenotype and function. 28,37 Here, we found that the coculture of pNK cells with trophoblasts significantly increased Th2-type cytokine production and decreased Th1-type cytokine and perforin expression by pNK cells. This makes pNK cells more adaptable to a dNK cell phenotype.…”

“…30 These NK cells experience modulation by trophoblasts after enrichment at the maternal-fetal interface. 37 Because Tim-3 was detected on peripheral NK cells and dNK cells in early pregnancy, we speculated here that the Gal-9/Tim-3 pathway may participate in the instruction of pNK cells by trophoblasts. We first determined the expression of Gal-9 in placental trophoblasts.…”

PECULIARITIES OF NK CELLS DIFFERENTIATION: CD56dim AND CD56bright NK CELLS AT PREGNANCY AND IN NON-PREGNANT STATE

“…It was demonstrated that among decidual cells compared to NK cells of peripheral blood many more cells expressed receptor CD25 [33]. At that, more than half of cells present in decidua and expressing CD25 are NK cells, while in peripheral blood, T-lymphocytes make up the majority of CD25 + cells [33]. For NK cells of peripheral blood with CD3 -CD56 bright CD25…”

“…+ phenotype the reduced expression of inhibiting receptors and increased expression of activation receptors is typical, as well as reduced content of perforin and granzyme B and increased expression of IFNγ and TGF-β [33]. It is supposed that these NK cells can migrate into the uterus and their main function is to secrete cytokines and maintain cytokine microenvironment in the zone of uteroplacental bed at pregnancy [33].…”

“…It is supposed that these NK cells can migrate into the uterus and their main function is to secrete cytokines and maintain cytokine microenvironment in the zone of uteroplacental bed at pregnancy [33]. However, at …”