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Natural killer cells promote fetal development through the secretion of growth-promoting factors

ABSTRACT: Natural killer (NK) cells are present in large populations at the maternal-fetal interface during early pregnancy, but their roles in fetal growth are unclear. Here, we identify a CD49a+Eomes+ subset of NK cells that have the capability to secrete growth-promoting-factors (GPF), including pleiotrophin, osteoglycin and osteopontin in both humans and mice. Decreases in this GPF-secreting NK subset impair fetal development, and leads to fetal growth restriction. The transcriptional factor Nfil3 but not T-bet affects the function and the number of this decidual NK subset. The crosstalk of the HLA-G-ILT2-KIR2DL4 axis promotes the GPF-secreting function of this NK subset. Adoptive transfer of these induced CD49a+Eomes+NK cells can reverse the impaired fetal growth and rebuild an appropriate local microenvironment. These findings reveal new properties of NK cells in promoting fetal growth as well as novel approaches for therapeutically administering NK cells to reverse restricted nourishments within the microenvironment during early pregnancy. To investigate novel molecular signatures of human decidual NK cells, we performed microarray analysis on dNK cells (CD3−CD56+CD49a+CD49b−) and pNK cells (CD3−CD56+CD49a−CD49b+). dNK cells were purified from first-trimester deciduas. pNK cells were purified from adult peripheral blood mononuclear cells. Samples were collected from healthy adult donors after obtaining informed consent according to the Ethics Committee of the University of Science & Technology of China. Overall design: We performed human microarray analysis on purified NK cells from normal human decidua during the first trimester of pregnancy; peripheral blood NK cells were used as controls.

INSTRUMENT(S): [PrimeView] Affymetrix Human Gene Expression Array

SUBMITTER: Zhou Yonggang  

PROVIDER: GSE97217 | GEO | 2018-01-04



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Natural Killer Cells Promote Fetal Development through the Secretion of Growth-Promoting Factors.

Fu Binqing B   Zhou Yonggang Y   Ni Xiang X   Tong Xianhong X   Xu Xiuxiu X   Dong Zhongjun Z   Sun Rui R   Tian Zhigang Z   Wei Haiming H  

Immunity 20171201 6

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  ...[more]

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