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Abstract
Dendritic cell (DC) and natural killer (NK) cell interactions are important for the regulation of innate and adaptive immunity, but their relevance during early pregnancy remains elusive. Using two different strategies to manipulate the frequency of NK cells and DC during gestation, we investigated their relative impact on the decidualization process and on angiogenic responses that characterize murine implantation. Manipulation of the frequency of NK cells, DC or both lead to a defective decidual response characterized by decreased proliferation and differentiation of stromal cells. Whereas no detrimental effects were evident upon expansion of DC, NK cell ablation in such expanded DC mice severely compromised decidual development and led to early pregnancy loss. Pregnancy failure in these mice was associated with an unbalanced production of anti-angiogenic signals and most notably, with increased expression of genes related to inflammation and immunogenic activation of DC. Thus, NK cells appear to play an important role counteracting potential anomalies raised by DC expansion and overactivity in the decidua, becoming critical for normal pregnancy progression.
Highlights
The early events taking place at the mouse and human endometrium following implantation determine the most critical period for successful mammalian pregnancy
To investigate whether this cooperation occurs in vivo, we aimed at comparing pregnancy progression upon combined administration of diphtheria toxin (DT), which selectively depletes Dendritic cell (DC) in CD11c.diphteria toxin receptor (DTR) transgenic mice, with anti-asialo GM1 antibody treatment for natural killer (NK) cell depletion [6,20] at the onset of implantation (Fig. 1A)
We provide novel insights about the regulatory role played by NK cells in preventing potential anomalies due to excessive DC activation during early pregnancy
Summary
The early events taking place at the mouse and human endometrium following implantation determine the most critical period for successful mammalian pregnancy. In view of the importance of DC derived signals for the normal functions of the NK cell pool, the severe defects associated with DC depletion may reflect a disruption of cooperative effects mediated by both cell subsets. This is consistent with findings from in vitro studies showing that trophoblasts fail to induce a proliferative response in uterine cell cultures depleted of DC and NK cells [9]
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