Human leukocyte antigen HLA-C, HLA-G, HLA-F, and HLA-E placental profiles are altered in early severe preeclampsia and preterm birth with chorioamnionitis

Dunk, Caroline; Bucher, Matthew; Zhang, Jianhong; Hayder, Heyam; Geraghty, Daniel E.; Lye, Stephen J.; Myatt, Leslie; Hackmon, Rinat

doi:10.1016/j.ajog.2022.07.021

Cited by 9 publications

(9 citation statements)

References 62 publications

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“…Considering that EVTs have also expressed other HLA molecules, such as HLA-C, -E, and -F, attention should be paid to the interaction between them. The above trophoblastic HLA molecules are mentioned in a recent study of placental villous tissues ( 41 ). HLA-G and -C were more highly expressed in PE, whereas HLA-E and -F were reduced.…”

Section: Discussionmentioning

confidence: 99%

Application of a JEG-3 organoid model to study HLA-G function in the trophoblast

et al. 2023

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The human placenta is a unique temporary organ with a mysterious immune tolerance. The formation of trophoblast organoids has advanced the study of placental development. HLA-G is uniquely expressed in the extravillous trophoblast (EVT) and has been linked to placental disorders. With older experimental methodologies, the role of HLA-G in trophoblast function beyond immunomodulation is still contested, as is its role during trophoblast differentiation. Organoid models incorporating CRISPR/Cas9 technology were used to examine the role of HLA-G in trophoblast function and differentiation. JEG-3 trophoblast organoids (JEG-3-ORGs) were established that highly expressed trophoblast representative markers and had the capacity to differentiate into EVT. CRISPR/Cas9 based on HLA-G knockout (KO) significantly altered the trophoblast immunomodulatory effect on the cytotoxicity of natural killer cells, as well as the trophoblast regulatory effect on HUVEC angiogenesis, but had no effect on the proliferation and invasion of JEG-3 cells and the formation of TB-ORGs. RNA-sequencing analysis further demonstrated that JEG-3 KO cells followed similar biological pathways as their wild-type counterparts during the formation of TB-ORGs. In addition, neither HLA-G KO nor the exogenous addition of HLA-G protein during EVT differentiation from JEG-3-ORGs altered the temporal expression of the known EVT marker genes. Based on the JEG-3 KO (disruption of exons 2 and 3) cell line and the TB-ORGs model, it was determined that HLA-G has a negligible effect on trophoblast invasion and differentiation. Despite this, JEG-3-ORG remains a valuable model for studying trophoblast differentiation.

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Section: Discussionmentioning

confidence: 99%

Application of a JEG-3 organoid model to study HLA-G function in the trophoblast

et al. 2023

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“…HLA-G is exclusively expressed in extravillous trophoblast cells ( 18 , 19 ). It can be present in seven isoforms, four membrane-bound (m) isoforms (mHLA-G: HLA-G1, -G2, -G3 and -G4) and three soluble (s) isoforms (sHLA-G: HLA-G5, -G6 and -G7).…”

Section: Immunomodulatory Effect Of Hla-gmentioning

confidence: 99%

“…In the process of reproductive immunity, HLA-E plays a protective role in the earliest events of implantation but not in active EVT invasion ( 19 ). HLA E mainly down-regulate the immune response at the maternal-fetal interface by cooperating with classical HLA class I molecules to ensure the success of pregnancy.…”

Section: Immunomodulatory Effect Of Hla-ementioning

confidence: 99%

“…HLA-F is expressed throughout pregnancy, and the expression increases with the passage of pregnancy time ( 93 , 94 ). Its abnormally low expression (compared with healthy pregnant women) will lead to many diseases, such as Intrahepatic Cholestasis of Pregnancy (ICP), gestational hypertension, preeclampsia and gestational diabetes mellitus ( 19 ). These diseases are also closely related to low expression of HLA-G and HLA-E ( 95 – 99 ).…”

Section: Immunomodulatory Effect Of Hla-fmentioning

confidence: 99%

“…Therefore, when HLA-Ib expressed by the fetal trophoblast cells, they are unlikely to be seen as foreign by the maternal immune system. Furthermore, it is certain that when the body has an inflammatory reaction, the level of HLA in maternal serum will be affected ( 19 ). This indicates that the expression of HLA Ib is similar to other classic HLA molecules and will be affected by the inflammatory reaction.…”

Section: Immunomodulatory Effect Of Hla-fmentioning

confidence: 99%

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Advances in the study of HLA class Ib in maternal-fetal immune tolerance

et al. 2022

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The HLA class Ib molecule is an alloantigen that causes transplant rejection on behalf of individual human and plays an important role in maternal-fetal immune tolerance. Early studies on HLA class Ib focused on the mechanism of HLA-G-induced immune escape, but in recent years, studies on the mechanism of HLA-G have deepened and gradually explored the mechanism of HLA-E and HLA-F, which are also HLA class Ib molecules. In the maternal-fetal interface, trophoblast cells express HLA class Ib molecules to protect the fetus from maternal immune cells by binding to inhibitory receptors of decidual immune cells (DICs) and shifting Th1/Th2 balance toward Th2 bias. Further studies on the molecular mechanism of HLA class Ib molecules provide a reference for its application in the field of clinical assisted reproduction.

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The Identification of Key Genes and Biological Pathways in Polycystic Ovary Syndrome and its Complications by Next Generation Squancing (NGS) and Bioinformatics Analysis

Vastrad¹,

Vastrad²

2023

Preprint

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Polycystic ovary syndrome (PCOS) is is associated with infertility, obesity, insulin resistance, hyperinsulinemia, type 2 diabetes mellitus, hypertension, cardiovascular problems, neurological and psychological problems and cancer. The specific mechanism of PCOS and its complications remains unclear. The aim of this study was to apply a bioinformatics approach to reveal related pathways or genes involved in the development of PCOS and its complications. The next generation squancing (NGS) datset GSE199225 was downloaded from the gene expression omnibus (GEO) database. Differentially expressed gene (DEG) analysis was performed using DESeq2. The g:Profiler was utilized to analyze the functional enrichment, gene ontology (GO) and REACTOME pathway of the differentially expressed genes. A protein-protein interaction (PPI) network was constructed and module analysis was performed using HiPPIE and cytoscape. The miRNA-hub gene regulatory network and TF-hub gene regulatory network were also constructed for research. The expression of the hub genes was validated using receiver operating characteristic (ROC) curve analysis. We have identified 957 DEGs in total, including 478 up regulated genes and 479 down regulated gene. GO and REACTOME illustrated that DEGs in PCOS were significantly enriched in regulation of molecular function, developmental process, interferon signaling and platelet activation, signaling and aggregation. Finally, through analyzing the PPI network, modules, miRNA-hub gene regulatory network and TF-hub gene regulatory network, we screened hub genes HSPA5, PLK1, RIN3, DBN1, CCDC85B, DISC1, AR, MTUS2, LYN and TCF4 by the Cytoscape software. This study uses a series of bioinformatics technologies to obtain hug genes and key pathways related to PCOS and its complications. These analysis results provide us with novel ideas for finding biomarkers and treatment methods for PCOS and its complications.

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Human leukocyte antigen HLA-C, HLA-G, HLA-F, and HLA-E placental profiles are altered in early severe preeclampsia and preterm birth with chorioamnionitis

Cited by 9 publications

References 62 publications

Application of a JEG-3 organoid model to study HLA-G function in the trophoblast

Application of a JEG-3 organoid model to study HLA-G function in the trophoblast

Advances in the study of HLA class Ib in maternal-fetal immune tolerance

The Identification of Key Genes and Biological Pathways in Polycystic Ovary Syndrome and its Complications by Next Generation Squancing (NGS) and Bioinformatics Analysis

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