Uterine NK cells are critical in shaping DC immunogenic functions compatible with pregnancy progression.
Uterine NK cells are critical in shaping DC immunogenic functions compatible with pregnancy progression.
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DOI：
10.1371/journal.pone.0046755
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Blois SM
中科院分区：
文献类型：
--
作者：
Tirado-González I;Barrientos G;Freitag N;Otto T;Thijssen VL;Moschansky P;von Kwiatkowski P;Klapp BF;Winterhager E;Bauersachs S;Blois SM
树突状细胞（DC）和自然杀伤（NK）细胞的相互作用是重要的先天性和适应性免疫的调节，但它们在怀孕早期的相关性仍然难以捉摸。使用两种不同的策略来操纵NK细胞和DC在妊娠期间的频率，我们研究了它们对蜕膜化过程和表征小鼠植入的血管生成反应的相对影响。操纵NK细胞、DC或两者的频率会导致以基质细胞增殖和分化减少为特征的有缺陷的蜕膜反应。虽然在DC扩增后没有明显的有害影响，但在这种扩增的DC小鼠中的NK细胞消融严重损害了蜕膜发育并导致早期妊娠丢失。这些小鼠的妊娠失败与抗血管生成信号的不平衡产生有关，最值得注意的是，与炎症和DC免疫原性激活相关的基因表达增加。因此，NK细胞似乎在对抗由蜕膜中DC扩增和过度活性引起的潜在异常中发挥重要作用，对正常妊娠进展至关重要。
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.
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