Human CD56bright NK cells accumulate in the maternal decidua during pregnancy and are found in direct contact with fetal trophoblasts. Several mechanisms have been proposed to explain the inability of NK cells to kill the semiallogeneic fetal cells. However, the actual functions of decidual NK (dNK) cells during pregnancy are mostly unknown. Here we show that dNK cells, but not peripheral blood–derived NK subsets, regulate trophoblast invasion both in vitro and in vivo by production of the interleukin-8 and interferon-inducible protein–10 chemokines. Furthermore, dNK cells are potent secretors of an array of angiogenic factors and induce vascular growth in the decidua. Notably, such functions are regulated by specific interactions between dNK-activating and dNK-inhibitory receptors and their ligands, uniquely expressed at the fetal-maternal interface. The overall results support a 'peaceful' model for reproductive immunology, in which elements of innate immunity have been incorporated in a constructive manner to support reproductive tissue development.
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We would like to thank O. Wald, N. Stern, G. Cohen, G. Katz, T. Gonen-Gross and S. Cohen for assistance. We would like to also thank I. Ariel and A. Peled for discussion. O.M. is supported by research grants from the Israel Cancer Research Foundation, The Israel Science Foundation, European Commission (QLK2-CT-2002-011112) and the Israeli Cancer Research Institute. S.Y. is supported by a grant from the Office of the Chief Scientist, Israel Ministry of Health (5695). J.H. is supported by fellowships from the Foulkes Foundation and Israeli Ministry of Education.
The authors declare no competing financial interests.
Chemokine receptor expression on human invasive trophoblasts. (PDF 57 kb)
Characterization of dNK clones for LIR and KIR expression. (PDF 62 kb)
Average normalized values obtained from genearray analysis on human dNK cells. (XLS 2779 kb)
Transcription profile of selected chemokines and angiogenic factors in dNK cells revealed by microarray analysis. (PDF 68 kb)
Semiquantative RT-PCR analysis of chemokines in human dNK cells. (PDF 79 kb)
Chemokine receptor transcription on HLA-G+ purified human invasive decidual trophoblasts. (PDF 56 kb)
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Hanna, J., Goldman-Wohl, D., Hamani, Y. et al. Decidual NK cells regulate key developmental processes at the human fetal-maternal interface. Nat Med 12, 1065–1074 (2006). https://doi.org/10.1038/nm1452
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