Journal
JOURNAL OF IMMUNOLOGY
Volume 182, Issue 7, Pages 4085-4092Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.0803769
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Funding
- National Institutes of Health
- National Institute on Environmental Sciences [P20RR018728]
- Superfund Basic Research Program Award [P42ES013660]
- National Institutes of Health [AI51877]
- Fogarty International Center [FIC 2D43TW006807]
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Although replete with cytotoxic machinery, uterine NK (uNK) cells remain tolerant at the maternal-fetal interface. The mechanisms that facilitate the uNK cell tolerance are largely unknown. In this study, we demonstrate that vascular endothelial growth factor (VEGF) C, a proangiogenic factor produced by uNK cells, is responsible for their noncytotoxic activity. VEGF C-producing uNK cells support endovascular processes as demonstrated in a three-dimensional coculture model of capillary tube formation on Matrigel. Peripheral blood NK cells fail to produce VEGF C and remain cytotoxic. This response can be reversed by exogenous VEGF C. We chow that cytoprotection by VEGF C can be related to induction of the TAP-1 expression and MHC class I assembly in target cells-Small interfering RNA-mediated silencing of TAP-1 expression abolished the VEGF C-imparted protection. Overall, these results demonstrate that empowerment of uNK cells with angiogenic factors keeps them noncytotoxic. This phenotype is critical to their pregnancy-compatible immunovascular role during placentation and fetal development. The Journal of Immunology, 2009, 182: 4085-4092.
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