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Decidual natural killer cell receptor expression is altered in pregnancies with impaired vascular remodeling and a higher risk of pre-eclampsia.

Wallace AE, Whitley GS, Thilaganathan B, Cartwright JE - J. Leukoc. Biol. (2014)

Bottom Line: We have used flow cytometry to examine dNK cells isolated from these pregnancies compared with those from pregnancies with a normal RI.We report a reduction in the proportion of dNK cells from high RI pregnancies expressing KIR2DL/S1,3,5 and LILRB1, receptors for HLA-C and HLA-G on trophoblast.These results indicate that dNK cells from high RI pregnancies may display altered interactions with trophoblast via decreased expression of HLA-binding cell-surface receptors, impacting on successful transformation of the uterus for pregnancy.

View Article: PubMed Central - PubMed

Affiliation: Institute of Cardiovascular and Cell Sciences, St George's University of London, United Kingdom; and.

ABSTRACT
During pregnancy, a specialized type of NK cell accumulates in the lining of the uterus (decidua) and interacts with semiallogeneic fetal trophoblast cells. dNK cells are functionally and phenotypically distinct from PB NK and are implicated in regulation of trophoblast transformation of the uterine spiral arteries, which if inadequately performed, can result in pregnancy disorders. Here, we have used uterine artery Doppler RI in the first trimester of pregnancy as a proxy measure of the extent of transformation of the spiral arteries to identify pregnancies with a high RI, indicative of impaired spiral artery remodeling. We have used flow cytometry to examine dNK cells isolated from these pregnancies compared with those from pregnancies with a normal RI. We report a reduction in the proportion of dNK cells from high RI pregnancies expressing KIR2DL/S1,3,5 and LILRB1, receptors for HLA-C and HLA-G on trophoblast. Decreased LILRB1 expression in the decidua was examined by receptor blocking in trophoblast coculture and altered dNK expression of the cytokines CXCL10 and TNF-α, which regulate trophoblast behavior. These results indicate that dNK cells from high RI pregnancies may display altered interactions with trophoblast via decreased expression of HLA-binding cell-surface receptors, impacting on successful transformation of the uterus for pregnancy.

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Cytokine mRNA expression in normal RI dNK cells in coculture with SGHPL-4cells after blocking of LILRB1.Normal RI dNK cells were cocultured with sHLA-G-SGHPL-4 cells for 6 h andcollected. Cytokine expression was analyzed by qRT-PCR of (A) TNF, (B) CXCL10,(C) IFN-γ, (D) PLGF, (E) IL-8. Data shown are mean foldchange ± sem relative to IgG control.*P < 0.05; n = 6.
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Figure 5: Cytokine mRNA expression in normal RI dNK cells in coculture with SGHPL-4cells after blocking of LILRB1.Normal RI dNK cells were cocultured with sHLA-G-SGHPL-4 cells for 6 h andcollected. Cytokine expression was analyzed by qRT-PCR of (A) TNF, (B) CXCL10,(C) IFN-γ, (D) PLGF, (E) IL-8. Data shown are mean foldchange ± sem relative to IgG control.*P < 0.05; n = 6.

Mentions: A decrease in expression of LILRB1 may lead to a decreased capacity to bind ligand ontrophoblast. To determine if this altered dNK cell activity, dNK cells from normal RIpregnancies (to ensure a larger proportion of LILRB1-expressing dNK cells) werecocultured with an EVT cell line overexpressing HLA-G [23], and the LILRB1 blocked with a blocking antibody. Cytokineproduction in dNK cells was measured by PCR (Fig.5). Expression of TNF-α was found to beincreased in dNK cells with decreased LILRB1 binding capacity (Fig. 5A; P < 0.05), and expression ofCXCL10 was found to be decreased (Fig. 5B;P < 0.05). Expression of three other cytokines shown to beimportant in dNK-trophoblast interactions—IFN-γ, PLGF,and IL-8—did not alter (Fig.5C–E).


Decidual natural killer cell receptor expression is altered in pregnancies with impaired vascular remodeling and a higher risk of pre-eclampsia.

Wallace AE, Whitley GS, Thilaganathan B, Cartwright JE - J. Leukoc. Biol. (2014)

Cytokine mRNA expression in normal RI dNK cells in coculture with SGHPL-4cells after blocking of LILRB1.Normal RI dNK cells were cocultured with sHLA-G-SGHPL-4 cells for 6 h andcollected. Cytokine expression was analyzed by qRT-PCR of (A) TNF, (B) CXCL10,(C) IFN-γ, (D) PLGF, (E) IL-8. Data shown are mean foldchange ± sem relative to IgG control.*P < 0.05; n = 6.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4377829&req=5

Figure 5: Cytokine mRNA expression in normal RI dNK cells in coculture with SGHPL-4cells after blocking of LILRB1.Normal RI dNK cells were cocultured with sHLA-G-SGHPL-4 cells for 6 h andcollected. Cytokine expression was analyzed by qRT-PCR of (A) TNF, (B) CXCL10,(C) IFN-γ, (D) PLGF, (E) IL-8. Data shown are mean foldchange ± sem relative to IgG control.*P < 0.05; n = 6.
Mentions: A decrease in expression of LILRB1 may lead to a decreased capacity to bind ligand ontrophoblast. To determine if this altered dNK cell activity, dNK cells from normal RIpregnancies (to ensure a larger proportion of LILRB1-expressing dNK cells) werecocultured with an EVT cell line overexpressing HLA-G [23], and the LILRB1 blocked with a blocking antibody. Cytokineproduction in dNK cells was measured by PCR (Fig.5). Expression of TNF-α was found to beincreased in dNK cells with decreased LILRB1 binding capacity (Fig. 5A; P < 0.05), and expression ofCXCL10 was found to be decreased (Fig. 5B;P < 0.05). Expression of three other cytokines shown to beimportant in dNK-trophoblast interactions—IFN-γ, PLGF,and IL-8—did not alter (Fig.5C–E).

Bottom Line: We have used flow cytometry to examine dNK cells isolated from these pregnancies compared with those from pregnancies with a normal RI.We report a reduction in the proportion of dNK cells from high RI pregnancies expressing KIR2DL/S1,3,5 and LILRB1, receptors for HLA-C and HLA-G on trophoblast.These results indicate that dNK cells from high RI pregnancies may display altered interactions with trophoblast via decreased expression of HLA-binding cell-surface receptors, impacting on successful transformation of the uterus for pregnancy.

View Article: PubMed Central - PubMed

Affiliation: Institute of Cardiovascular and Cell Sciences, St George's University of London, United Kingdom; and.

ABSTRACT
During pregnancy, a specialized type of NK cell accumulates in the lining of the uterus (decidua) and interacts with semiallogeneic fetal trophoblast cells. dNK cells are functionally and phenotypically distinct from PB NK and are implicated in regulation of trophoblast transformation of the uterine spiral arteries, which if inadequately performed, can result in pregnancy disorders. Here, we have used uterine artery Doppler RI in the first trimester of pregnancy as a proxy measure of the extent of transformation of the spiral arteries to identify pregnancies with a high RI, indicative of impaired spiral artery remodeling. We have used flow cytometry to examine dNK cells isolated from these pregnancies compared with those from pregnancies with a normal RI. We report a reduction in the proportion of dNK cells from high RI pregnancies expressing KIR2DL/S1,3,5 and LILRB1, receptors for HLA-C and HLA-G on trophoblast. Decreased LILRB1 expression in the decidua was examined by receptor blocking in trophoblast coculture and altered dNK expression of the cytokines CXCL10 and TNF-α, which regulate trophoblast behavior. These results indicate that dNK cells from high RI pregnancies may display altered interactions with trophoblast via decreased expression of HLA-binding cell-surface receptors, impacting on successful transformation of the uterus for pregnancy.

Show MeSH
Related in: MedlinePlus