NK cells specialize in killing tumor cells and virally infected cells and also possess non-cytotoxic functions, which include secretion of a variety of cytokines and growth factors. Their activity is mediated by a vast repertoire of inhibitory and activating NK receptors. Recently, it was demonstrated that ligation of the Notch receptor plays a significant role not only in T cell development but also in human T cell and mouse NK cell activation. However, the involvement of Notch triggering in human NK cell activity has not yet been determined. Here we show that Notch1 and Notch2, but not Notch3 and Notch 4, are expressed in human peripheral blood NK cells and in decidual NK cells. We demonstrate that in peripheral blood NK cells only the Notch ligand Delta4 could interact with Notch, whereas in decidual NK cells both Delta1 and Delta4 can interact with Notch. Finally, we show that Notch activation in these cells leads to increased secretion of IFNγ. We therefore present here a new function of the Notch receptors as enhancers of peripheral blood NK cell and decidual NK cell functions.
Bibliographical noteFunding Information:
This study was supported by grants from the Israeli Cancer Research Foundation, The Israeli Science Foundation, The ISF (Morasha), The Rosenkratz foundation, The European Consortium (MRTN-CT-2005 and LSCH-CT-2005-518178) and by the Association for International Cancer Research AICR (all to O.M). O.M. is a Crown professor of Molecular Immunology. We thank Dr. Tom Kadesch for providing us with the Delta4 and Jagged1-Fc plasmids. We thank Dr. Spyros Artavanis-Tsakonas for providing us with the cDNA of Delta1.
- Cytokine secretion
- Decidual NK cells
- Notch receptor
- Peripheral blood NK cells