Killer Immunoglobulin-Like Receptor 2DL4 (CD158d) Regulates Human Mast Cells Both Positively and Negatively: Possible Roles in Pregnancy and Cancer Metastasis

Killer immunoglobulin-like receptor (KIR) 2DL4 (CD158d) was previously thought to be a human NK-cell-specific protein but its expression has also been demonstrated in human mast cells. Mast cells are involved in allergic reactions via their KIT-mediated and IgE receptor-mediated responses. We recently detected the expression of KIR2DL4 in human cultured mast cells established from peripheral blood derived from healthy volunteers (PB-mast), a human mast cell line (LAD2), and non-neoplastic mast cells, including pathological specimens. An agonistic antibody against KIR2DL4 negatively regulates the KIT- and IgE-receptor-mediated responses of PB-mast and LAD2 cells. In addition, agonistic antibodies and human leukocyte antigen (HLA)-G, a natural ligand for KIR2DL4, induce the secretion from these cells of leukemia inhibitory factor and serine proteases, which have been implicated in pregnancy establishment and cancer metastasis. Therefore, KIR2DL4 stimulation with agonistic antibodies and recombinant HLA-G protein may enhance both processes, in addition to suppressing mast-cell-mediated allergic reactions.