The alteration of placental-derived soluble MHC class I chain-related protein A and B during pregnancy

Huang, Shih-Yin; Cw, Chiang; Chen, Fangping; Yu, Chia‐Li

doi:10.1111/j.1600-0412.2011.01131.x

Cited by 9 publications

(7 citation statements)

References 24 publications

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“…Interestingly, levels of the protein encoded by MICB fall prior to parturition. 53 Pathway analysis of genes with correlated expression levels (FDR < 0.05) were consistent with the results of those performed with correlated CpG sites (data not shown).…”

Section: Correlation Between Maternal and Fetal Gene Expressionsupporting

confidence: 88%

“…For example, MICB is part of the MHC class I chain and is induced by cellular stress to initiate an immune response. 53 Activation of inflammatory pathways has been implicated in the timing of parturition specifically in PTB, 11 and we observed lower methylation of CpGs in MICB in PTB as well as correlated methylation and expression patterns in maternal-fetal pairs. These results suggest a complex relationship between sequence variation, DNA methylation, and gene expression that should be considered in future studies of PTB.…”

Section: Discussionsupporting

confidence: 50%

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DNA methylation provides insight into intergenerational risk for preterm birth in African Americans

et al. 2015

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Abbreviations: DOHaD, developmental origin of health and disease; FDR, false discovery rate; GA, gestational age; PTB, preterm birth; SES, socioeconomic status.African Americans are at increased risk for spontaneous preterm birth (PTB). Though PTB is heritable, genetic studies have not identified variants that account for its intergenerational risk, prompting the hypothesis that epigenetic factors may also contribute. The objective of this study was to evaluate DNA methylation from maternal leukocytes to identify patterns specific to PTB and its intergenerational risk. DNA from peripheral leukocytes from African American women that delivered preterm (24-34 weeks; N D 16) or at term (39-41 weeks; N D 24) was assessed for DNA methylation using the HumanMethylation450 BeadChip. In maternal samples, 17,829 CpG sites associated with PTB, but no CpG site remained associated after correction for multiple comparisons. Examination of paired maternal-fetal samples identified 5,171 CpG sites in which methylation of maternal samples correlated with methylation of her respective fetus (FDR < 0.05). These correlated sites were enriched for association with PTB in maternal leukocytes. The majority of correlated CpG sites could be attributed to one or more genetic variants. They were also significantly more likely to be in genes involved in metabolic, cardiovascular, and immune pathways, suggesting a role for genetic and environmental contributions to PTB risk and chronic disease. The results of this study may provide insight into the factors underlying intergenerational risk for PTB and its consequences.

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Section: Correlation Between Maternal and Fetal Gene Expressionsupporting

confidence: 88%

Section: Discussionsupporting

confidence: 50%

DNA methylation provides insight into intergenerational risk for preterm birth in African Americans

et al. 2015

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“…sMIC was also reported as a novel blood biomarker of the chances of a viable baby in infertile women undergoing in vitro fertilization (Porcu-Buisson et al, 2007). Consistent with these reports is the finding of reduced production of sMICA by the aged placenta playing a role in parturition (Huang et al, 2011).…”

Section: Pregnancysupporting

confidence: 77%

MICA (MHC class I polypeptide-related sequence A)

Ahmed¹,

Askar²

2017

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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Human Major Histocompatibility Complex (MHC) Class I Chain-Related gene A (MICA) is located 46 Kb centromeric to the HLA-B locus on the short arm of human chromosome 6 and encodes for a 62-kda cell surface glycoprotein. It is expressed on endothelial cells, dendritic cells, fibroblasts, epithelial cells, and many tumours and serves as target for both cellular and humoral immune responses in transformed cells. MICA protein at normal states has a low level of expression in epithelial tissues but is upregulated in response to various stimuli of cellular stress. MICA also functions as a ligand recognized by the activating receptor NKG2D that is expressed on the surface of NK, NKT, CD8+ and TCRγδ+ T cells. Allelic variants of MICA due to a single amino acid substitution at position 129 in the α2 domain have been reported to result in large differences in NKG2D binding. These variable affinities have been suggested to affect thresholds of NK cell triggering and T cell modulation in autoimmune diseases and malignancies. MICA molecules exist also in soluble forms (sMICA) and altered serum levels of sMICA have been reported in multiple states of health and disease.

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“…Levels of sNKG2DLs were highest during the second trimester, perhaps due to increasing size of the placenta, but fell to significantly lower levels in the third trimester. The serum levels of soluble MIC in pregnant and nonpregnant women were confirmed in an independent study where the authors postulated the decline of sMIC toward full‐term represented a proinflammatory trigger leading to parturition . The Mincheva‐Nilsson group then published a more detailed study showing STB cells secrete sNKG2DLs via exosomes, which expressed not only sMICA and sMICB but also sULBP1‐5 or in other words, all NKG2DLs known at that time.…”

Section: Discussionmentioning

confidence: 85%

Umbilical cord blood plasma contains soluble NKG2D ligands that mediate loss of natural killer cell function and cytotoxicity

et al. 2015

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NK cells play a key role in innate elimination of virally infected or neoplastic cells but they can be circumvented by immunoevasive mechanisms enabling viral spread or tumor progression. Engagement of the NKG2D activating receptor with soluble forms of itsligand is one such mechanism of inducing NK cell hyporesponsiveness. Interestingly, this immunoevasive strategy among others is described at the maternal-fetal interface where tolerance of the semi-allogeneic fetus is required to allow successful human pregnancy. Understanding of maternal-fetal tolerance is increasing but mechanisms preventing alloreactivity of fetal immune cells against the maternal host are less well understood. The study of umbilical cord blood has enabled insight of the fetal immune system, which appears immature and inert. We have found that soluble NKG2D ligands (sNKG2DLs) are present in cord blood plasma (CBP) and associate with adult NK cell hyporesponsiveness demonstrated by reduced CD107a expression and secretion of IFN-γ upon stimulation. The capacity of NK cells to kill K562 cells or proliferate was also reduced by incubation with CBP; however, physical removal of sNKG2DL from CBP restored K562 lytic function and NKG2D expression. Therefore, our results strongly suggest sNKG2DLs are expressed in CBP as a mechanism of fetal-maternal tolerance in human pregnancy. Keywords:Ligand r NK cell r NKG2D r Pregnancy r Tolerance Additional supporting information may be found in the online version of this article at the publisher's web-site Eur. J. Immunol. 2015Immunol. . 45: 2324Immunol. -2334 Innate immunity 2325 group 2, member D receptor (NKG2D) on infected and tumor cells [4,5]. NKG2D is a C-type lectin-like molecule and interaction with its cognate ligand expressed on stressed cells results in direct cytolysis and cytokine production [6]. Immunoevasive strategies allow some viruses and tumors to escape detection by intracellular retention of NKG2D ligands (NKG2DLs) [7]. Alternatively, soluble NKG2DLs (sNKG2DLs) can be released from the cell surface as free-soluble molecules by protease cleavage or by secretion on exosomes [5]. NKG2D is expressed on NKT cells, γδ + T cells and CD8 + T cells as well as NK cells. Interaction with sNKG2DLs leads to downregulation of this receptor, rendering the cell hyporesponsive [8,9]. There are eight known types of NKG2DLs that divide into two groups; [10,11] the highly polymorphic MHC class Irelated chain A and B (MICA/B) and the unique long 16 binding proteins (ULBP1-6), which are also polymorphic [12][13][14][15]. It is probable that viral and possibly tumor immunity has shaped evolution of NKG2DLs in an effort to combat immunoevasive strategies targeting NKG2D. Human pregnancy presents a unique immunological dilemma as the fetus is semiallogeneic and a potential target for destruction by maternal T cells recognizing paternal antigens on placental trophoblast cells [16]. Maternal T-cell responses against trophoblasts are limited by unusual expression of MHC class I antigens by the various trophoblast...

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The alteration of placental-derived soluble MHC class I chain-related protein A and B during pregnancy

Cited by 9 publications

References 24 publications

DNA methylation provides insight into intergenerational risk for preterm birth in African Americans

DNA methylation provides insight into intergenerational risk for preterm birth in African Americans

MICA (MHC class I polypeptide-related sequence A)

Umbilical cord blood plasma contains soluble NKG2D ligands that mediate loss of natural killer cell function and cytotoxicity

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