Neutrophils in pregnancy: New insights into innate and adaptive immune regulation

Bert, Serena; Ward, Emily M. Geraghty; Nadkarni, Suchita

doi:10.1111/imm.13392

Cited by 29 publications

(24 citation statements)

References 113 publications

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“…Fetal immune system development was a special process. Placental microenvironment and pregnancy hormones play a key role in shaping the phenotype, function, metabolism and transcription of neutrophils in UCB ( 21 , 22 ). They are the reasons for the different genotypes of neutrophils in UCB compared to healthy adults.…”

Section: Discussionmentioning

confidence: 99%

Primitive genotypic characteristics in umbilical cord neutrophils identified by single-cell transcriptome profiling and functional prediction

Chen

Huang²,

Guo³

et al. 2022

Front. Immunol.

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The function and heterogeneity of neutrophils in neonatal umbilical cord blood (UCB) have not been characterized. In this study, we analyzed the neutrophils in UCB and healthy adults using single-cell RNA sequencing analysis for the first time. We found that neutrophils divided into six subpopulations (G2, G3, G4, G5a, G5b, and G5c) with different marker genes and different functions under homeostasis. Compared with healthy adults, neutrophils of UCB were more naïve and have more obvious degranulation and activation functions. Moreover, we found significant differences in the amount and function of G5b cells between healthy adults and UCB. The amount of G5b group in UCB was lower, but it has more degranulation, secretion and activation functions. In addition, we noted a new subset of G5c labeled by CD52, which almost did not exist in UCB. Besides, its differential genes were enriched in terms such as protein synthesis and mRNA transcription. Furthermore, uncharacteristic transcription factors ZNF-276, ZNF-319 and ZNF-354A were identified in our study. In summary, we first examined the heterogeneity and functional diversity of neutrophils in UCB, and these data provided new insights into the mechanism of neutrophil-mediated diseases of neonates and the wider use of neutrophils in UCB.

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Section: Discussionmentioning

confidence: 99%

Primitive genotypic characteristics in umbilical cord neutrophils identified by single-cell transcriptome profiling and functional prediction

Chen

Huang²,

Guo³

et al. 2022

Front. Immunol.

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“…These cells are programmed to secrete pro-inflammatory cytokines and growth factors regulating decidua receptiveness and most importantly maternal resistance to embryo invasion [39]. It seems that cytokines orchestrate an immunological balancing between inflammatory and anti-inflammatory responses and are required for establishing maternal tolerance to the semi-allogenic fetus as well as for protecting both the mother and the fetus from infections throughout pregnancy [40,41]. Thus, many fetal, maternal, and placental mechanisms work simultaneously and synchronously establishing embryo-maternal communication in order to support embryo implantation and pregnancy establishment [42].…”

Section: Basic Immunological Characteristics Of the Endometrial Micro...mentioning

confidence: 99%

The Role of Interleukins in Recurrent Implantation Failure: A Comprehensive Review of the Literature

Pantos¹,

Grigoriadis

Maziotis

et al. 2022

IJMS

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Recurrent implantation failure (RIF) is a multifactorial condition affecting 10–15% of in vitro fertilization (IVF) couples. Data suggest that functional dysregulation of the endometrial immune system constitutes one of the main pathophysiological mechanisms leading to RIF. The aim of this article is to provide a thorough presentation and evaluation of the role of interleukins (ILs) in the pathogenesis of RIF. A comprehensive literature screening was performed summarizing current evidence. During implantation, several classes of ILs are secreted by epithelial and stromal endometrial cells, including IL-6, IL-10, IL-12, IL-15, IL-18, and the leukemia inhibitory factor. These ILs create a perplexing network that orchestrates both proliferation and maturation of uterine natural killer cells, controls the function of regulatory T and B cells inhibiting the secretion of antifetal antibodies, and supports trophoblast invasion and decidua formation. The existing data indicate associations between ILs and RIF. The extensive analysis performed herein concludes that the dysregulation of the ILs network indeed jeopardizes implantation leading to RIF. This review further proposes a mapping of future research on how to move forward from mere associations to robust molecular data that will allow an accurate profiling of ILs in turn enabling evidence-based consultancy and decision making when addressing RIF patients.

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“…Single-cell transcriptomics revealed that decidualized assembloids harbored senescent subpopulations, and senescence in the stroma calibrated the emergence of anti-inflammatory decidual cells and pro-inflammatory senescent decidual cells, which controlled endometrial fate decisions at implantation and was closely correlated with RIF ( 15 ). Moreover, intricate immune regulation is one of the most crucial aspects for the successful implantation of the hemiallogenic embryo ( 16 , 17 ). Conversely, inappropriate immunocytes as well as immune function are implicated in RIF as evidenced by increasing high-quality studies ( 18 ).…”

Section: Introductionmentioning

confidence: 99%

Deciphering the endometrial immune landscape of RIF during the window of implantation from cellular senescence by integrated bioinformatics analysis and machine learning

Zhao

Zhao²,

Jiang³

et al. 2022

Front. Immunol.

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Recurrent implantation failure (RIF) is an extremely thorny issue in in-vitro fertilization (IVF)-embryo transfer (ET). However, its intricate etiology and pathological mechanisms are still unclear. Nowadays, there has been extensive interest in cellular senescence in RIF, and its involvement in endometrial immune characteristics during the window of implantation (WOI) has captured scholars’ growing concerns. Therefore, this study aims to probe into the pathological mechanism of RIF from cellular senescence and investigate the correlation between cellular senescence and endometrial immune characteristics during WOI based on bioinformatics combined with machine learning strategy, so as to elucidate the underlying pathological mechanisms of RIF and to explore novel treatment strategies for RIF. Firstly, the gene sets of GSE26787 and GSE111974 from the Gene Expression Omnibus (GEO) database were included for the weighted gene correlation network analysis (WGCNA), from which we concluded that the genes of the core module were closely related to cell fate decision and immune regulation. Subsequently, we identified 25 cellular senescence-associated differentially expressed genes (DEGs) in RIF by intersecting DEGs with cellular senescence-associated genes from the Cell Senescence (CellAge) database. Moreover, functional enrichment analysis was conducted to further reveal the specific molecular mechanisms by which these molecules regulate cellular senescence and immune pathways. Then, eight signature genes were determined by the machine learning method of support vector machine-recursive feature elimination (SVM-RFE), random forest (RF), and artificial neural network (ANN), comprising LATS1, EHF, DUSP16, ADCK5, PATZ1, DEK, MAP2K1, and ETS2, which were also validated in the testing gene set (GSE106602). Furthermore, distinct immune microenvironment abnormalities in the RIF endometrium during WOI were comprehensively explored and validated in GSE106602, including infiltrating immunocytes, immune function, and the expression profiling of human leukocyte antigen (HLA) genes and immune checkpoint genes. Moreover, the correlation between the eight signature genes with the endometrial immune landscape of RIF was also evaluated. After that, two distinct subtypes with significantly distinct immune infiltration characteristics were identified by consensus clustering analysis based on the eight signature genes. Finally, a “KEGG pathway–RIF signature genes–immune landscape” association network was constructed to intuitively uncover their connection. In conclusion, this study demonstrated that cellular senescence might play a pushing role in the pathological mechanism of RIF, which might be closely related to its impact on the immune microenvironment during the WOI phase. The exploration of the molecular mechanism of cellular senescence in RIF is expected to bring new breakthroughs for disease diagnosis and treatment strategies.

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Neutrophils in pregnancy: New insights into innate and adaptive immune regulation

Cited by 29 publications

References 113 publications

Primitive genotypic characteristics in umbilical cord neutrophils identified by single-cell transcriptome profiling and functional prediction

Primitive genotypic characteristics in umbilical cord neutrophils identified by single-cell transcriptome profiling and functional prediction

The Role of Interleukins in Recurrent Implantation Failure: A Comprehensive Review of the Literature

Deciphering the endometrial immune landscape of RIF during the window of implantation from cellular senescence by integrated bioinformatics analysis and machine learning

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