|Maternal NK enable extravillous cytotrophoblasts to converge with epithelial cells of spiral arteries|
|Single cell analysis at the Fetal - Maternal interface|
Maternal decidual NK cells that transfer into the developing placenta probably remain less cytolyic. Given the active environment they may even be metabolically exhausted, but are still capable of lytic activity and could play a critical role eliminating aberrant cells of the rapidly developing embryo. Further this activity could also educate fetal NK cells that start to develop from 6 weeks. Because this exposure occurs during early development of the fetal immune system, the primary response is to develop allospecific tolerance to maternal antigens.
A new concept is emerging in that the uterine immune system uses NK cell allorecognition to regulate placentation and to control the maternofetal interface. The jury is still out on microchimeric influences including exosomes, DNA and whole cells that transfer between mother and fetus. However, it seems entirely plausible that maternal immune cells may do much more than we presently know to shape conditions and determine cells of the fetus.
Our research interest relates to p53 peptides presented by MHC class receptors on targets of NK cells. We maintain the well conserved phospho-acceptor sites of p53 protein in axis with MDM2 is central to immunity and allorecognition. It is known that p53 plays an important role in blastocyst implantation and maternal reproduction through regulation of leukemia inhibitory factor (LIF) in mice. We expect p53 peptides, influenced by transcription regulatory factors determine outcomes of immune-target reactions including blastocyst implantation. Further that TP53 transcription can be triggered in a target by NK allorecognition nano-probe at a distance resulting in target p53 peptide presentation by MHC as NK's go-no-go cytolytic tipping point for immunity.