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Reproduction (Cambridge, England) Jun 2024The mechanism underlying the accumulation of γδT cells in the decidua, which helps maintain maternal-fetal immunotolerance in early pregnancy, is unknown. This study...
IN BRIEF
The mechanism underlying the accumulation of γδT cells in the decidua, which helps maintain maternal-fetal immunotolerance in early pregnancy, is unknown. This study reveals that DSC-derived RANKL upregulates ICAM-1 expression via the NF-κB pathway to enable γδT cell accumulation in the early decidua.
ABSTRACT
Decidual γδT (dγδT) cells help maintain maternal-fetal immunotolerance in early pregnancy. However, the mechanism underlying the accumulation of γδT cells in the decidua is unknown. Previous work showed that RANKL upregulated intercellular adhesion molecule 1 (ICAM-1) in decidual stromal cells (DSCs), and Rankl knockout mice had limited dγδT cell populations. In this study, we measured the expression levels of RANKL/RANK and ICAM-1 in DSCs, in addition to the integrins of ICAM-1 on dγδT cells, and the number of dγδT cells from patients with recurrent spontaneous abortion (RSA) and normal pregnant women in the first trimester. RSA patients showed significantly decreased RANKL/RANK and ICAM-1/CD11a signaling in decidua, and a decreased percentage of dγδT cells, which was positively correlated with DSC-derived RANKL and ICAM-1. Next, an in vitro adhesion experiment showed that the enhanced attraction of human DSCs to dγδT cells after RANKL overexpression was almost completely aborted by anti-ICAM-1. Furthermore, Rankl knockout mice showed a significant reduction in NF-κB activity compared with wild-type controls. Finally, we applied a selective NF-κB inhibitor named PDTC to validate the role of NF-κB in RANKL-mediated ICAM-1 upregulation. Taken together, our data show that DSC-derived RANKL upregulates ICAM-1 expression via the NF-κB pathway to enable γδT cell accumulation in the early decidua. A reduction in RANKL/ICAM-1 signaling in DSCs may result in insufficient accumulation of γδT cells in decidua and, in turn, RSA.
Topics: Adult; Animals; Female; Humans; Mice; Pregnancy; Decidua; Intercellular Adhesion Molecule-1; Mice, Knockout; NF-kappa B; RANK Ligand; Receptors, Antigen, T-Cell, gamma-delta; Signal Transduction; Stromal Cells; T-Lymphocytes; Up-Regulation
PubMed: 38614129
DOI: 10.1530/REP-23-0262 -
Cellular and Molecular Life Sciences :... Apr 2024Aberrant remodeling of uterine spiral arteries (SPA) is strongly associated with the pathogenesis of early-onset preeclampsia (EOPE). However, the complexities of SPA...
Aberrant remodeling of uterine spiral arteries (SPA) is strongly associated with the pathogenesis of early-onset preeclampsia (EOPE). However, the complexities of SPA transformation remain inadequately understood. We conducted a single-cell RNA sequencing analysis of whole placental tissues derived from patients with EOPE and their corresponding controls, identified DAB2 as a key gene of interest and explored the mechanism underlying the communication between Extravillous trophoblast cells (EVTs) and decidual vascular smooth muscle cells (dVSMC) through cell models and a placenta-decidua coculture (PDC) model in vitro. DAB2 enhanced the motility and viability of HTR-8/SVneo cells. After exposure to conditioned medium (CM) from HTR-8/SVneo cells, hVSMCs exhibited a rounded morphology, indicative of dedifferentiation, while CM-HTR-8/SVneo cells displayed a spindle-like morphology. Furthermore, the PDC model demonstrated that CM-HTR-8/SVneo was less conducive to vascular remodeling. Further in-depth mechanistic investigations revealed that C-X-C motif chemokine ligand 8 (CXCL8, also known as IL8) is a pivotal regulator governing the dedifferentiation of dVSMC. DAB2 expression in EVTs is critical for orchestrating the phenotypic transition and motility of dVSMC. These processes may be intricately linked to the CXCL8/PI3K/AKT pathway, underscoring its central role in intricate SPA remodeling.
Topics: Pregnancy; Humans; Female; Interleukin-8; Phosphatidylinositol 3-Kinases; Pre-Eclampsia; Placenta; Arteries; Culture Media, Conditioned; Adaptor Proteins, Signal Transducing; Apoptosis Regulatory Proteins; Eosine Yellowish-(YS); Phosphatidylethanolamines
PubMed: 38613672
DOI: 10.1007/s00018-024-05212-4 -
Frontiers in Immunology 2024During pregnancy, the maternal immune system must allow and support the growth of the developing placenta while maintaining the integrity of the mother's body. The...
During pregnancy, the maternal immune system must allow and support the growth of the developing placenta while maintaining the integrity of the mother's body. The trophoblast's unique HLA signature is a key factor in this physiological process. This study focuses on decidual γδT cell populations and examines their expression of receptors that bind to non-classical HLA molecules, HLA-E and HLA-G. We demonstrate that decidual γδT cell subsets, including Vδ1, Vδ2, and double-negative (DN) Vδ1-/Vδ2- cells express HLA-specific regulatory receptors, such as NKG2C, NKG2A, ILT2, and KIR2DL4, each with varying dominance. Furthermore, decidual γδT cells produce cytokines (G-CSF, FGF2) and cytotoxic mediators (Granulysin, IFN-γ), suggesting functions in placental growth and pathogen defense. However, these processes seem to be controlled by factors other than trophoblast-derived non-classical HLA molecules. These findings indicate that decidual γδT cells have the potential to actively contribute to the maintenance of healthy human pregnancy.
Topics: Pregnancy; Humans; Female; Placenta; Decidua; HLA-G Antigens; Trophoblasts; Cytokines; Antineoplastic Agents
PubMed: 38601161
DOI: 10.3389/fimmu.2024.1382424 -
Frontiers in Immunology 2024Natural killer (NK) cells, with a unique NK cell receptor phenotype, are abundantly present in the non-pregnant (endometrium) and pregnant (decidua) humanuterine mucosa....
Natural killer (NK) cells, with a unique NK cell receptor phenotype, are abundantly present in the non-pregnant (endometrium) and pregnant (decidua) humanuterine mucosa. It is hypothesized that NK cells in the endometrium are precursors for decidual NK cells present during pregnancy. Microenvironmental changes can alter the phenotype of NK cells, but it is unclear whether decidual NK cell precursors in the endometrium alter their NK cell receptor repertoire under the influence of pregnancy. To examine whether decidual NK cell precursors reveal phenotypic modifications upon pregnancy, we immunophenotyped the NK cell receptor repertoire of both endometrial and early-pregnancy decidual NK cells using flow cytometry. We showed that NK cells in pre-pregnancy endometrium have a different phenotypic composition compared to NK cells in early-pregnancy decidua. The frequency of killer-immunoglobulin-like receptor (KIR expressing NK cells, especially KIR2DS1, KIR2DL2L3S2, and KIR2DL2S2 was significantly lower in decidua, while the frequency of NK cells expressing activating receptors NKG2D, NKp30, NKp46, and CD244 was significantly higher compared to endometrium. Furthermore, co-expression patterns showed a lower frequency of NK cells co-expressing KIR3DL1S1 and KIR2DL2L3S2 in decidua. Our results provide new insights into the adaptations in NK cell receptor repertoire composition that NK cells in the uterine mucosa undergo upon pregnancy.
Topics: Pregnancy; Female; Humans; Receptors, Natural Killer Cell; Endometrium; Killer Cells, Natural; Uterus; Mucous Membrane
PubMed: 38571943
DOI: 10.3389/fimmu.2024.1353556 -
Persoonia Jun 2023Novel species of fungi described in this study include those from various countries as follows: , on whitefly, on bark of , from soil under , on leaf spot of , and...
Novel species of fungi described in this study include those from various countries as follows: , on whitefly, on bark of , from soil under , on leaf spot of , and on leaf spot of . , on fully submersed siliceous schist in high-mountain streams, and on the lower part and apothecial discs of on a twig. , on decaying wood, from moist soil with leaf litter, on a trunk of a living unknown hardwood tree species, and on dead twigs of unidentified plant. , on sandy soil in a plantation of . , on dead bark of , and on dead bark of . , on fruit lesion of . , on corticioid , on sp. , on calcareous soils in dry forests and park habitats. , on sandy soil under , and on leaves of . , on decaying bark of logs, on unidentified woody substrate, from soil, on the trunk of , and on elephant dung. , on infected leaves of . , (incl. gen. nov.) from . , on acidic soil. , on dead leaf of , and on dead leaves of . , on dead culms of , (incl. gen. nov.) on culms of , (incl. gen. nov.) on branch of , on dead standing culms of , on culms of , and on dead bamboo sticks. , half-buried and moss-covered pieces of rotting wood in grass-grown path. , on soil. , (incl. gen. nov.) from resin of ssp. , from sooty mould community on , and from a gallery of on . , on mossy areas of laurel forest areas planted with , and from a biofilm covering a biodeteriorated limestone wall. , from hypersaline sea water, and from water sample collected from hypersaline lagoon. , on culm of , on , (incl. gen. nov.) on culms of , on nest of cases of bag worm moths () on , on leaves of , on stems of , from the roots of × , and (incl. gen. nov.) on leaf of . , on decaying leaves of sp. from pond. , on the bark of fallen trees of , from surface-sterilised, asymptomatic roots of , on soil in mixed forest, on calcareous soil in mixed forest, on acidic soils, from roots of × , on leaves of sp., and from soil. , on calcareous soil. , on pupa, buried in soil, on larva, buried in soil, and on pupa, buried in soil. , on dead leaf of . , on clay loamy soils. , (incl. gen. nov.) on leaves of . , on recently dead stem of , (incl. gen. nov.) from water, and from swab of coil surface. Morphological and culture characteristics for these new taxa are supported by DNA barcodes. : Crous PW, Osieck ER, Shivas RG, et al. 2023. Fungal Planet description sheets: 1478-1549. Persoonia 50: 158- 310. https://doi.org/10.3767/persoonia.2023.50.05.
PubMed: 38567263
DOI: 10.3767/persoonia.2023.50.05 -
Frontiers in Immunology 2024Prior to pregnancy, hormonal changes lead to cellular adaptations in the endometrium allowing for embryo implantation. Critical for successful pregnancy establishment,...
INTRODUCTION
Prior to pregnancy, hormonal changes lead to cellular adaptations in the endometrium allowing for embryo implantation. Critical for successful pregnancy establishment, innate immune cells constitute a significant proportion of uterine cells prior to arrival of the embryo and throughout the first trimester in humans and animal models. Abnormal uterine immune cell function during implantation is believed to play a role in multiple adverse pregnancy outcomes. Current work in humans has focused on uterine immune cells present after pregnancy establishment, and limited in vitro models exist to explore unique functions of these cells.
METHODS
With single-cell RNA-sequencing (scRNAseq), we comprehensively compared the human uterine immune landscape of the endometrium during the window of implantation and the decidua during the first trimester of pregnancy.
RESULTS
We uncovered global and cell-type-specific gene signatures for each timepoint. Immune cells in the endometrium prior to implantation expressed genes associated with immune metabolism, division, and activation. In contrast, we observed widespread interferon signaling during the first trimester of pregnancy. We also provide evidence of specific inflammatory pathways enriched in pre- and post-implantation macrophages and natural killer (NK) cells in the uterine lining. Using our novel implantation-on-a-chip (IOC) to model human implantation ex vivo, we demonstrate for the first time that uterine macrophages strongly promote invasion of extravillous trophoblasts (EVTs), a process essential for pregnancy establishment. Pre- and post-implantation uterine macrophages promoted EVT invasion to a similar degree as pre- and post-implantation NK cells on the IOC.
CONCLUSIONS
This work provides a foundation for further investigation of the individual roles of uterine immune cell subtypes present prior to embryo implantation and during early pregnancy, which will be critical for our understanding of pregnancy complications associated with abnormal trophoblast invasion and placentation.
Topics: Pregnancy; Female; Animals; Humans; Decidua; Embryo Implantation; Uterus; Killer Cells, Natural; Macrophages
PubMed: 38566989
DOI: 10.3389/fimmu.2024.1364036 -
Scientific Reports Apr 2024Decidualization can be induced by culturing human endometrial stromal cells (ESCs) with several decidualization stimuli, such as cAMP, medroxyprogesterone acetate (MPA)...
Decidualization can be induced by culturing human endometrial stromal cells (ESCs) with several decidualization stimuli, such as cAMP, medroxyprogesterone acetate (MPA) or Estradiol (E). However, it has been unclear how decidualized cells induced by different stimuli are different. We compared transcriptomes and cellular functions of decidualized ESCs induced by different stimuli (MPA, E + MPA, cAMP, and cAMP + MPA). We also investigated which decidualization stimulus induces a closer in vivo decidualization. Differentially expressed genes (DEGs) and altered cellular functions by each decidualization stimuli were identified by RNA-sequence and gene-ontology analysis. DEGs was about two times higher for stimuli that use cAMP (cAMP and cAMP + MPA) than for stimuli that did not use cAMP (MPA and E + MPA). cAMP-using stimuli altered the cellular functions including angiogenesis, inflammation, immune system, and embryo implantation whereas MPA-using stimuli (MPA, E + MPA, and cAMP + MPA) altered the cellular functions associated with insulin signaling. A public single-cell RNA-sequence data of the human endometrium was utilized to analyze in vivo decidualization. The altered cellular functions by in vivo decidualization were close to those observed by cAMP + MPA-induced decidualization. In conclusion, decidualized cells induced by different stimuli have different transcriptome and cellular functions. cAMP + MPA may induce a decidualization most closely to in vivo decidualization.
Topics: Female; Humans; Cells, Cultured; Endometrium; Medroxyprogesterone Acetate; Stromal Cells; Gene Expression; RNA; Decidua
PubMed: 38565619
DOI: 10.1038/s41598-024-58065-z -
Epigenetics Dec 2024Decidual macrophages are the second-largest immune cell group at the maternal-foetal interface. They participate in apoptotic cell removal, and protect the foetus from...
Decidual macrophages are the second-largest immune cell group at the maternal-foetal interface. They participate in apoptotic cell removal, and protect the foetus from microorganisms or pathogens. Dysfunction of decidual macrophages gives rise to pregnancy complications such as preeclampsia and recurrent spontaneous miscarriage (RSM). However, the mechanisms by which decidual macrophages are involved in the occurrence of adverse pregnancy outcomes have not been elucidated. Here we integrated DNA methylation and gene expression data from decidua macrophages to identify potential risk factors related to RSM. was significantly hypomethylated and upregulated in decidual macrophages from RSM patients. Further demethylation analysis demonstrated that expression in decidual macrophages was significantly increased by 5-Aza-dC treatment. In addition, the influence of GPR133 on the phagocytic ability of macrophages was explored. Phagocytosis was impaired in the decidual macrophages of RSM patients with increased expression. Increased expression induced by demethylation treatment in the decidual macrophages of healthy control patients led to a significant decrease in phagocytic function. Importantly, knockdown of resulted in a significant improvement in the phagocytic function of THP-1 macrophages. In conclusion, the existing studies have shown the influence of on the phagocytic function of decidual macrophages and pregnancy outcomes, providing new data and ideas for future research on the role of decidual macrophages in RSM.
Topics: Female; Humans; Pregnancy; Abortion, Spontaneous; Decidua; DNA Methylation; Macrophages; Phagocytosis; Up-Regulation
PubMed: 38564758
DOI: 10.1080/15592294.2024.2337087 -
Journal of Reproductive Immunology Jun 2024Pre-eclampsia (PE) is a hypertension condition that occurs exclusively during pregnancy and has the potential to impact nearly all organ systems. It is estimated to... (Review)
Review
Pre-eclampsia (PE) is a hypertension condition that occurs exclusively during pregnancy and has the potential to impact nearly all organ systems. It is estimated to complicate approximately 2-8% of pregnancies worldwide. PE is a prominent medical disorder that poses a significant risk to pregnant mothers and their infants. This review commences by giving the most up-to- date concepts about the pathophysiology of PE. The condition involves atypical infiltration of trophoblast cells into the spiral arteries of the decidua and myometrium, resulting in an insufficient establishment of proper blood flow between the uterus and placenta. The aberrant activation of natural killer (NK) cells in both the peripheral blood and the decidua has been identified as one of the contributing factors to the development of PE. The strong evidence for the genetic etiology of PE is provided by the association between maternal killer cell immunoglobulin-like receptor (KIR) and Human Leukocyte Antigen (HLA-C) in trophoblast cells. Recent observations provide evidence that changes in the expression of anti-angiogenic factors in the placenta are the underlying cause of the clinical symptoms associated with the condition. This review also provides a comprehensive overview of the latest advancements in understanding the underlying causes of PE. It specifically highlights the emergence of new diagnostic biomarkers and their potential implications for therapeutic interventions in managing this medical condition.
Topics: Humans; Pre-Eclampsia; Pregnancy; Female; Biomarkers; Killer Cells, Natural; Trophoblasts; Receptors, KIR; Placenta; HLA-C Antigens; Animals; Decidua
PubMed: 38555746
DOI: 10.1016/j.jri.2024.104236 -
Journal of Clinical Pathology Mar 2024A hydatidiform mole (HM) is classified as complete (CHM) or partial (PHM) based on its morphology and genomic composition. Ancillary techniques are often required to...
AIMS
A hydatidiform mole (HM) is classified as complete (CHM) or partial (PHM) based on its morphology and genomic composition. Ancillary techniques are often required to confirm a morphologically suspected PHM diagnosis. This study sought to evaluate the clinical accuracy of PHM diagnosis using morphological assessment supported by dual-colour dual-hapten in situ hybridisation (D-DISH) ploidy determination.
METHODS
Over a 2-year period, our unit examined 1265 products of conception (POCs) from which 103 atypical POCs were diagnosed as PHM or non-molar conceptuses with the assistance of D-DISH ploidy analysis. We retrospectively audited a sample of 40 of these atypical POCs using short tandem repeat genotyping. DNA extracted from formalin-fixed paraffin-embedded tissue was genotyped using 24 polymorphic loci. Parental alleles in placental villi were identified by comparison to those in maternal decidua. To identify triploid PHM cases, we sought three alleles of equal peak height or two alleles with one allele peak twice the height of the other at each locus.
RESULTS
Thirty-six of the 40 cases (19 PHM and 17 non-molar) were successfully genotyped and demonstrated complete concordance with the original diagnosis. All PHMs were diandric triploid of dispermic origin. In two non-molar diploid cases, we identified suspected trisomies (13 and 18), which potentially explains the pregnancy loss in these cases.
CONCLUSIONS
This study validates the use of D-DISH ploidy analysis to support the diagnosis of a morphologically suspected PHM in our practice.
PubMed: 38555105
DOI: 10.1136/jcp-2023-209269