Human Decidual NK Cells: Unique Phenotype and Functional Properties – A Review

Tabiasco, Julie; Rabot, Magali; Aguerre-Girr, Maryse; ElCosta, H; Berrébi, Alain; Parant, Olivier; Laškarin, Gordana; Juretić, Koraljka; Bensussan, Armand; Rukavina, Daniel

doi:10.1016/j.placenta.2006.01.009

Cited by 126 publications

(93 citation statements)

References 53 publications

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“…Interestingly, most of dNK were CD160 neg whereas a minor subset appeared CD160 pos ( Fig. 1), contrasting again with PB-NK (19). Among the inhibitory receptors tested, all dNK expressed NKG2A: a complete shift of the whole dNK population was indeed observed, when compared with a negative control such as the CD160 neg subset (Control mean fluorescence intensity: 3, NKG2A mean fluorescence intensity: 14).…”

Section: A Unique Identical Expression Of Activating and Inhibitorymentioning

confidence: 84%

Critical and Differential Roles of NKp46- and NKp30-Activating Receptors Expressed by Uterine NK Cells in Early Pregnancy

Costa

Casemayou

Aguerre-Girr

et al. 2008

The Journal of Immunology

128

150

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In early human pregnancy, uterine decidual NK cells (dNK) are abundant and considered as cytokine producers but poorly cytotoxic despite their cytolytic granule content, suggesting a negative control of this latter effector function. To investigate the basis of this control, we examined the relative contribution to the cytotoxic function of different activating receptors expressed by dNK. Using a multicolor flow cytometry analysis, we found that freshly isolated dNK exhibit a unique repertoire of activating and inhibitory receptors, identical among all the donors tested. We then demonstrated that in fresh dNK, mAb-specific engagement of NKp46-, and to a lesser extent NKG2C-, but not NKp30-activating receptors induced intracellular calcium mobilization, perforin polarization, granule exocytosis and efficient target cell lysis. NKp46-mediated cytotoxicity is coactivated by CD2 but dramatically blocked by NKG2A coengagement, indicating that the dNK cytotoxic potential could be tightly controlled in vivo. We finally found that in dNK, mAb-specific engagement of NKp30, but not NKp46, triggered the production of IFN-γ, TNF-α, MIP-1α, MIP-1β, and GM-CSF proinflammatory molecules. These data demonstrate a differential, controlled role of NKp46- and NKp30-activating receptors expressed by dNK that could be critical for the outcome of pregnancy and the killing of uterine cells infected by pathogens.

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Section: A Unique Identical Expression Of Activating and Inhibitorymentioning

confidence: 84%

Critical and Differential Roles of NKp46- and NKp30-Activating Receptors Expressed by Uterine NK Cells in Early Pregnancy

Costa

Casemayou

Aguerre-Girr

et al. 2008

The Journal of Immunology

128

150

View full text Add to dashboard Cite

show abstract

“…The analysis of eNK cells that is shown in this study was performed on freshly isolated, nonmanipulated endometrial lymphocytes, whereas the Sentman et al analysis was performed on IL-2-activated eNK clones. Furthermore, IL-2 is a cytokine that was shown not to be expressed in the tissue and therefore is not suitable for in vitro activation of eNK cells (39).…”

Section: Discussionmentioning

confidence: 99%

Endometrial NK Cells Are Special Immature Cells That Await Pregnancy

Manaster

Mizrahi

Goldman‐Wohl

et al. 2008

The Journal of Immunology

226

190

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NK cells populate the human endometrium before pregnancy. Unlike decidual NK cells that populate the decidua during pregnancy, the NK cells present in the human endometrium, before pregnancy, have not been fully characterized. In this study, we provide a detailed analysis of the origin, phenotype, and function of endometrial NK cells (eNK). We show that eNK cells have a unique receptor repertoire. In particular, they are negative for NKp30 and chemokine receptor expression, which distinguishes them from any other NK subset described so far. We further show that eNK cells lack NK-specific functional phenotype and activity such as cytokine secretion and cytotoxicity, before IL-15 stimulation. Following such stimulation, endometrial NK cells acquire phenotype and function that are similar to those of decidual NK cells. We therefore suggest that eNK cells are inactive cells (before IL-15 activation and in relation to the known NK activity) that are present in the endometrium before conception, waiting for pregnancy.

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“…By expressing multiple cell surface molecules, secreting a variety of soluble factors, and interacting with other cell subsets in decidua, dNK cells participate in maintaining maternal-fetal tolerance, trophoblast invasion and vascular remodeling. 15,16 Crosstalk between decidual NK cells and CD14…”

Section: Introductionmentioning

confidence: 99%

The Galectin-9/Tim-3 pathway is involved in the regulation of NK cell function at the maternal–fetal interface in early pregnancy

et al. 2015

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Decidual natural killer (dNK) cells actively participate in the establishment and maintenance of maternal-fetal immune tolerance and act as local guardians against infection. However, how dNK cells maintain the immune balance between tolerance and anti-infection immune responses during pregnancy remains unknown. Here, we demonstrated that the inhibitory molecule T-cell immunoglobulin domain and mucin domain-containing molecule-3 (Tim-3) are expressed on over 60% of dNK cells. Tim-3 1 dNK cells display higher interleukin (IL)-4 and lower tumor necrosis factor (TNF)-a and perforin production. Human trophoblast cells can induce the transformation of peripheral NK cells into a dNK-like phenotype via the secretion of galectin-9 (Gal-9) and the interaction between Gal-9 and Tim-3. In addition, trophoblasts inhibit lipopolysaccharide (LPS)-induced pro-inflammatory cytokine and perforin production by dNK cells, which can be attenuated by Tim-3 neutralizing antibodies. Interestingly, a decreased percentage of Tim-3-expressing dNK cells were observed in human miscarriages and murine abortion-prone models. Moreover, T helper (Th)2-type cytokines were decreased and Th1-type cytokines were increased in Tim-3 1 but not Tim-3 2 dNK cells from human and mouse miscarriages. Therefore, our results suggest that the Gal-9/Tim-3 signal is important for the regulation of dNK cell function, which is beneficial for the maintenance of a normal pregnancy.

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Human Decidual NK Cells: Unique Phenotype and Functional Properties – A Review

Cited by 126 publications

References 53 publications

Critical and Differential Roles of NKp46- and NKp30-Activating Receptors Expressed by Uterine NK Cells in Early Pregnancy

Critical and Differential Roles of NKp46- and NKp30-Activating Receptors Expressed by Uterine NK Cells in Early Pregnancy

Endometrial NK Cells Are Special Immature Cells That Await Pregnancy

The Galectin-9/Tim-3 pathway is involved in the regulation of NK cell function at the maternal–fetal interface in early pregnancy

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