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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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Percentage of dNK cells isolated from normal RI pregnancies and high RIpregnancies positive for receptors listed, as assessed by flowcytometry.Data shown are individual patient samples, mean ± sem;n = at least 19 normal RI; n = at least 10high RI. *P < 0.05.
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Figure 2: Percentage of dNK cells isolated from normal RI pregnancies and high RIpregnancies positive for receptors listed, as assessed by flowcytometry.Data shown are individual patient samples, mean ± sem;n = at least 19 normal RI; n = at least 10high RI. *P < 0.05.

Mentions: dNK cells have been shown previously to express the following receptors: KIR2DL1/S1,KIR2DL2/S2, NKp30, NKp46, LILRB1, NKG2A, NKG2C, NKG2D, CD160, CD9, and CD69 [14, 15,24, 25]. Examination of dNK cells (gating strategy; Fig. 1A), from normal RI and high RI pregnancies(indicative of poor spiral artery remodeling), determined that these receptors werepresent in each group (Fig. 1B; representativeflow data from normal RI individual). All receptors were expressed in the sameproportion in high RI and normal RI pregnancies, with the exception of KIR2DL/S1,3,5and LILRB1, which were expressed on a significantly lower proportion of dNK cellsfrom high RI pregnancies (P < 0.05; Fig. 2). Likewise, significantly decreased expressionof KIR2DL/S1,3,5 and LILRB1 was found by analysis of mean fluorescence intensity data(P < 0.05; Supplemental Fig. 1).


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)

Percentage of dNK cells isolated from normal RI pregnancies and high RIpregnancies positive for receptors listed, as assessed by flowcytometry.Data shown are individual patient samples, mean ± sem;n = at least 19 normal RI; n = at least 10high RI. *P < 0.05.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

Figure 2: Percentage of dNK cells isolated from normal RI pregnancies and high RIpregnancies positive for receptors listed, as assessed by flowcytometry.Data shown are individual patient samples, mean ± sem;n = at least 19 normal RI; n = at least 10high RI. *P < 0.05.
Mentions: dNK cells have been shown previously to express the following receptors: KIR2DL1/S1,KIR2DL2/S2, NKp30, NKp46, LILRB1, NKG2A, NKG2C, NKG2D, CD160, CD9, and CD69 [14, 15,24, 25]. Examination of dNK cells (gating strategy; Fig. 1A), from normal RI and high RI pregnancies(indicative of poor spiral artery remodeling), determined that these receptors werepresent in each group (Fig. 1B; representativeflow data from normal RI individual). All receptors were expressed in the sameproportion in high RI and normal RI pregnancies, with the exception of KIR2DL/S1,3,5and LILRB1, which were expressed on a significantly lower proportion of dNK cellsfrom high RI pregnancies (P < 0.05; Fig. 2). Likewise, significantly decreased expressionof KIR2DL/S1,3,5 and LILRB1 was found by analysis of mean fluorescence intensity data(P < 0.05; Supplemental Fig. 1).

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