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

Abstract

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.

Identification of immune cells and mRNA associated with prognosis of gastric cancer

“…Mast cells have the ability to facilitate tumor proliferation and invasion directly,and indirectly promote tumor proliferation and invasion by regulating tumor microenvironment [22], it may provide further evidence for Mast cells can be applied in the adjuvant treatment of mammary adenocarcinoma and melanoma [23]. Previous studies have shown that Th2 cells, T helper cells, and Mast cells may play key roles in the development and invasion of cancer [24][25][26][27], our studies show that these immune cells may play a role in gastric cancer.…”

KIR Receptors as Key Regulators of NK Cells Activity in Health and Disease

“…The possible participation in the initiation of pregnancy has been linked with the presence of the KIR2DL4 receptor. However, it is not conclusive as positive and no-effect studies can be found in the literature [ 89 , 90 ]. A recent meta-analysis of data from articles from the databases like Web of Science, PubMed, Scopus, Google Scholar, etc.…”

Development and Validation of An Immune Gene Set-Based Prognostic Signature in Cutaneous Melanoma

“…Tumor cells could escape immune surveillance by induction of KLRK1 ligand expression [30]. KIR2DL4 belongs to the killer cell immunoglobulin-like receptors, transmembrane glycoproteins expressed on the surface of NK cells and some subsets of T cells [31]. IL18RAP, an accessory subunit of the IL-18 receptor, can enhance IL-18-binding activity and is involved in IL-18-dependent signal transduction, leading to the activation of NF-κB and JNK pathways [32].…”