Vascular endothelial growth factor C facilitates immune tolerance and endovascular activity of human uterine NK cells at the maternal-fetal interface. Export

@article{citeulike:4221452, abstract = {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 show 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.}, author = {Kalkunte, S. S. and Mselle, T. F. and Norris, W. E. and Wira, C. R. and Sentman, C. L. and Sharma, S.}, citeulike-article-id = {4221452}, citeulike-linkout-0 = {http://dx.doi.org/10.4049/jimmunol.0803769}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/19299706}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=19299706}, day = {1}, doi = {10.4049/jimmunol.0803769}, issn = {1550-6606}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, keywords = {fetal, feto-maternal, immune, maternal, tolerance, vegf}, month = {April}, number = {7}, pages = {4085--4092}, posted-at = {2009-03-26 08:58:39}, priority = {2}, title = {Vascular endothelial growth factor C facilitates immune tolerance and endovascular activity of human uterine NK cells at the maternal-fetal interface.}, url = {http://dx.doi.org/10.4049/jimmunol.0803769}, volume = {182}, year = {2009} }

TY - JOUR ID - citeulike:4221452 L3 - citeulike-article-id:4221452 N2 - 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 show 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. IS - 7 JF - Journal of immunology (Baltimore, Md. : 1950) SN - 1550-6606 EP - 4092 TI - Vascular endothelial growth factor C facilitates immune tolerance and endovascular activity of human uterine NK cells at the maternal-fetal interface. VL - 182 SP - 4085 KW - fetal KW - feto-maternal KW - immune KW - maternal KW - tolerance KW - vegf AU - Kalkunte, SS AU - Mselle, TF AU - Norris, WE AU - Wira, CR AU - Sentman, CL AU - Sharma, S PY - 2009/04/01/ UR - http://dx.doi.org/10.4049/jimmunol.0803769 ER -