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

Kataoka, Tatsuki R.; Ueshima, Chiyuki; Hirata, Masahiro; Minamiguchi, Sachiko; Haga, Hironori

doi:10.3390/ijms21030954

Cited by 12 publications

(11 citation statements)

References 101 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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.…”

Section: Kir/hla Interaction In Pregnancy Complicationmentioning

confidence: 99%

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

Dębska-Zielkowska

Moszkowska

Zieliński

et al. 2021

Cells

View full text Add to dashboard Cite

Natural killer (NK) cells are part of the cellular immune response. They target mainly cancer and virally infected cells. To a high extent cytotoxic activity of NK cells is regulated inter alia by signals from killer immunoglobulin-like receptors (KIR). The major histocompatibility complex (MHC) class I molecules are important ligands for KIR receptors. Binding of ligands (such as MHC I) to the KIR receptors has the important role in solid organ or hematopoietic cell transplantation. Of note, the understanding of the relationship between KIR and MHC receptors may contribute to the improvement of transplant results. Donor-recipient matching, which also includes the KIR typing, may improve monitoring, individualize the treatment and allow for predicting possible effects after transplantation, such as the graft-versus-leukemia effect (GvL) or viral re-infection. There are also less evident implications of KIR/MHC matching, such as with pregnancy and cancer. In this review, we present the most relevant literature reports on the importance of the KIR/MHC relationship on NK cell activity and hematopoietic stem cell transplantation (HSCT)/solid organ transplantation (SOT) effects, the risk of allograft rejection, protection against post-transplant cytomegalovirus (CMV) infection, pregnancy complications, cancer and adoptive therapy with NK cells.

show abstract

Section: Kir/hla Interaction In Pregnancy Complicationmentioning

confidence: 99%

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

Dębska-Zielkowska

Moszkowska

Zieliński

et al. 2021

Cells

View full text Add to dashboard Cite

show abstract

“…These 'HLA-G/KIR2DL4' combinations are able to result in the production of pro-inflammatory cytokines like IFN-g for driving cells into an immunosuppressive phase (134). KIR2DL4 could be also observed in mast cells recently (135). It was involved in Janus kinase-signal transducer and activator of transcription (JAK/STAT) signaling pathway association with trophoblast invasion and angiopoiesis by HTR-8/SVneo cell line.…”

Section: Hla-g Acting In the Pregnancy Microenvironmentmentioning

confidence: 99%

HLA-G: An Important Mediator of Maternal-Fetal Immune-Tolerance

2021

View full text Add to dashboard Cite

Maternal-fetal immune-tolerance occurs throughout the whole gestational trimester, thus a mother can accept a genetically distinct fetus without immunological aggressive behavior. HLA-G, one of the non-classical HLA class I molecules, is restricted-expression at extravillous trophoblast. It can concordantly interact with various kinds of receptors mounted on maternally immune cells residing in the uterus (e.g. CD4+ T cells, CD8+ T cells, natural killer cells, macrophages, and dendritic cells) for maintaining immune homeostasis of the maternal-fetus interface. HLA-G is widely regarded as the pivotal protective factor for successful pregnancies. In the past 20 years, researches associated with HLA-G have been continually published. Indeed, HLA-G plays a mysterious role in the mechanism of maternal-fetal immune-tolerance. It can also be ectopically expressed on tumor cells, infected sites and other pathologic microenvironments to confer a significant local tolerance. Understanding the characteristics of HLA-G in immunologic tolerance is not only beneficial for pathological pregnancy, but also helpful to the therapy of other immune-related diseases, such as organ transplant rejection, tumor migration, and autoimmune disease. In this review, we describe the biological properties of HLA-G, then summarize our understanding of the mechanisms of fetomaternal immunologic tolerance and the difference from transplant tolerance. Furthermore, we will discuss how HLA-G contributes to the tolerogenic microenvironment during pregnancy. Finally, we hope to find some new aspects of HLA-G in fundamental research or clinical application for the future.

show abstract

“…Unlike other KIR receptors, the KIR2DL4 receptor has inhibitory and activator properties [21][22][23]. The KIR2DL4 receptor can be activated by recombinant HLA-G (major histocompatibility complex, class I, G)or agonistic antibodies, such as KIR2DL4 clones mAb 33 and mAb 181703 [24][25]. Stimulating the activator signals of NK cells increases their cytotoxicity.…”

Section: Introductionmentioning

confidence: 99%

The effects of KIR2DL4 stimulated NK-92 cells on the apoptotic pathways of HER2 + /HER-breast cancer cells

et al. 2023

View full text Add to dashboard Cite

Natural killer (NK) cells are immune cells that have attracted signi cant attention due to their cytotoxic properties. They are believed to be highly effective in cancer therapy. In this study, anti-KIR2DL4 (Killer cell Immunoglobulin like Receptor, 2 Ig Domains and Long cytoplasmic tail 4) was used to stimulate the NK-92 activator receptor to increase their cytotoxicity on breast cancer cell lines. Unstimulated and stimulated NK-92 cells (sNK-92) were cocultured with breast cancer (MCF-7 and SK-BR-3) and normal breast (MCF-12A) cell lines at 1:1, 1:5, and 1:10 (Target: Effector) ratios. The most effective cell cytotoxicity ratio (1:10) was used in the immunostaining and western blot assays to evaluate apoptosis pathway proteins. The sNK-92 cells showed higher cytotoxic activity on breast cancer cells than NK-92 cells. sNK-92 cells had a selective signi cant cytotoxicity effect on MCF-7 and SK-BR-3 cells but not MCF-12A cells. While sNK-92 cells were effective at all cell concentrations, they were most effective at a 1:10 ratio. Immunostaining and western blots showed signi cantly higher BAX, caspase 3, and caspase 9 protein levels in all breast cancer cell groups cocultured with sNK-92 than with NK-92 cells. NK-92 cells stimulated with KIR2DL4 showed elevated cytotoxic activity. The cytotoxic activity of sNK-92 cells on breast cancer cells is via apoptosis pathways. However, their effect on normal breast cells is limited. While the obtained data contains only basic information, additional clinical studies are needed to provide a basis for a new treatment model.

show abstract

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

Cited by 12 publications

References 101 publications

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

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

HLA-G: An Important Mediator of Maternal-Fetal Immune-Tolerance

The effects of KIR2DL4 stimulated NK-92 cells on the apoptotic pathways of HER2 + /HER-breast cancer cells

Contact Info

Product

Resources

About