Soluble HLA-G induces NF-kappaB activation in natural killer cells.

Human leukocyte antigen (HLA)-G is an immunomodulatory molecule discovered for the first time in the maternal-fetal interface. In cancer context, where high number of natural killer (NK) cells is described, the presence of HLA-G in its soluble form is thought to be essential for NK cells signaling. To evaluate intracellular signaling in NK cells upon HLA-G soluble forms stimulation, we investigate the role of soluble HLA-G (HLA-G5- and HLA-G1 shedding form) stimulation on classical nuclear factor (NF)-kappaB pathway activation. We reported that these two forms of soluble HLA-G could activate NF-kappaB in NK cells. NF-kappaB activation in NK cells does implicate neither phosphatidylinositol 3-kinase (PI3K) nor MEK (MAP kinase kinase) as demonstrated after specific inhibition experiments. We demonstrated elsewhere that NF-kappaB activation in NK cells is not implicated in cytotoxicity inhibition by HLA-G. Our findings may suggest the important role played by NF-kappaB activation after soluble HLA-G stimulation in other NK cells function.