Natural Killer Cells Promote Fetal Development through the Secretion of Growth-Promoting Factors
Natural Killer Cells Promote Fetal Development through the Secretion of Growth-Promoting Factors
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自然杀伤细胞通过分泌生长促进因子促进胎儿发育。
DOI：
10.1016/j.immuni.2017.11.018
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发表时间：
2017-12-19
期刊：
影响因子：
32.4
通讯作者：
Wei, Haiming
中科院分区：
文献类型：
--
作者：
Fu, Binqing;Zhou, Yonggang;Wei, Haiming
自然杀伤（NK）细胞在妊娠早期大量存在于母胎界面。然而，NK细胞在胎儿生长中的作用尚不清楚。在这里，我们已经确定了一个CD 49 a（+）Eomes（+）NK细胞的子集，分泌生长促进因子（GPFs），包括多效生长因子和骨甘肽，在人类和小鼠。HLA-G和ILT 2之间的串扰充当该NK细胞亚群的GPF分泌功能的刺激。这种分泌GPF的NK细胞亚群减少会损害胎儿发育，导致胎儿生长受限。转录因子Nfil 3（而不是T-bet）影响了该蜕膜NK细胞亚群的功能和数量。诱导的CD 49 a（+）Eomes（+）NK细胞的连续转移逆转了受损的胎儿生长并重建了适当的局部微环境。这些发现揭示了NK细胞促进胎儿生长的特性。此外，本研究提出了NK细胞治疗性给药的方法，以逆转妊娠早期子宫微环境内的限制性增殖。
Natural killer (NK) cells are present in large populations at the maternal-fetal interface during early pregnancy. However, the role of NK cells in fetal growth is unclear. Here, we have identified a CD49a(+)Eomes(+) subset of NK cells that secreted growth-promoting factors (GPFs), including pleiotrophin and osteoglycin, in both humans and mice. The crosstalk between HLA-G and ILT2 served as a stimulus for GPF-secreting function of this NK cell subset. Decreases in this GPF-secreting NK cell subset impaired fetal development, resulting in fetal growth restriction. The transcription factor Nfil3, but not T-bet, affected the function and the number of this decidual NK cell subset. Adoptive transfer of induced CD49a(+)Eomes(+) NK cells reversed impaired fetal growth and rebuilt an appropriate local microenvironment. These findings reveal properties of NK cells in promoting fetal growth. In addition, this research proposes approaches for therapeutic administration of NK cells in order to reverse restricted nourishments within the uterine microenvironment during early pregnancy.