Role of Decidual Natural Killer Cells in Human Pregnancy and Related Pregnancy Complications

Zhang, Xiuhong; Wei, Haiming

doi:10.3389/fimmu.2021.728291

Cited by 90 publications

(83 citation statements)

References 153 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It was shown that the number of cytotoxic uNK cell-surface receptors on uNK cells and increased number of immature uNK cells was upregulated in the endometrium of infertile females with endometriosis, compared to fertile females. Moreover, NKp44 expression on uNK cells was significantly increased in RIF patients and indicated that NK cells’ cytotoxicity may cause the recurrent implantation failure [ 39 , 40 , 41 ].…”

Section: Discussionmentioning

confidence: 99%

Characterization of Epigenetic and Molecular Factors in Endometrium of Females with Infertility

et al. 2022

View full text Add to dashboard Cite

Infertility is one of the most rapidly increasing global health concerns of the 21st century. Embryo quality and endometrial thickness and receptivity are the main factors for successful embryo implantation and pregnancy development. Nevertheless, until now, there has been a lack of understanding about the regulation of human endometrium function and its structure. This raises the demand for more research of the human endometrium in these fields. In our study, we analyzed the genetic and epigenetic changes of endometrial tissue’s samples isolated from females admitted for treatment due to male infertility and females diagnosed with reproductive pathologies, who are preparing for assisted reproductive technologies procedures. Using real-time polymerase chain reaction method, we demonstrated that endometrium of females with reproductive pathology has significantly upregulated decidualization related genes HAND2, MUC1, CSF2, increased expression of angiogenesis related gene PDGFA, and increases of overall immune response and inflammation-related genes expression with significant changes of RELA and CXCL10 genes expression. Females with reproductive pathology have altered endometrium epigenetic regulation since expression of miRNAs—specifically, miRNA-34a, miRNA-223, and miRNA-125b—is lower in endometrium of females with reproductive pathology. Our findings suggest that the potential changes in genetic and epigenetic profile of endometrium from females with reproductive pathology could enrich the knowledge in the field of core biological knowledge and treatment of reproductive impairments.

show abstract

Section: Discussionmentioning

confidence: 99%

Characterization of Epigenetic and Molecular Factors in Endometrium of Females with Infertility

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Physiologically, dNK cells are crucial to successful placentation through the orchestration of trophoblast invasion and endometrial vasculature remodelling. Although not entirely understood, dNK cells are thought to be important for the induction of immune tolerance and maintaining a tolerogenic environment at the maternal decidua ( 47 ). Given their specialised nature, it is no surprise that dNK cells have a unique functional phenotype.…”

Section: Phenotype and Function Of Tissue-resident Nk Cellsmentioning

confidence: 99%

“…Most notably, dNK cells produce an array of pro-angiogenic factors such as vascular endothelial growth factor (VEGF), placental growth factor (PIGF), and angiopoietin-2 (Ang-2). In addition, dNK cells produce various immunoregulatory cytokines such as, transforming growth factor beta (TGFβ), GM-CSF, IL-8, and IL-10 ( 47 ), and are poorly cytolytic ( 46 ). Considering this, tumor-infiltrating NK cells displaying a dNK-like phenotype are unlikely to result in beneficial disease outcomes ( Figure 2 ).…”

Section: Phenotype and Function Of Tissue-resident Nk Cellsmentioning

confidence: 99%

Plasticity of NK cells in Cancer

2022

View full text Add to dashboard Cite

Natural killer (NK) cells are crucial to various facets of human immunity and function through direct cytotoxicity or via orchestration of the broader immune response. NK cells exist across a wide range of functional and phenotypic identities. Murine and human studies have revealed that NK cells possess substantial plasticity and can alter their function and phenotype in response to external signals. NK cells also play a critical role in tumor immunity and form the basis for many emerging immunotherapeutic approaches. NK cells can directly target and lyse malignant cells with their inherent cytotoxic capabilities. In addition to direct targeting of malignant cells, certain subsets of NK cells can mediate antibody-dependent cellular cytotoxicity (ADCC) which is integral to some forms of immune checkpoint-blockade immunotherapy. Another important feature of various NK cell subsets is to co-ordinate anti-tumor immune responses by recruiting adaptive and innate leukocytes. However, given the diverse range of NK cell identities it is unsurprising that both pro-tumoral and anti-tumoral NK cell subsets have been described. Here, NK cell subsets have been shown to promote angiogenesis, drive inflammation and immune evasion in the tumor microenvironment. To date, the signals that drive tumor-infiltrating NK cells towards the acquisition of a pro- or anti-tumoral function are poorly understood. The notion of tumor microenvironment-driven NK cell plasticity has substantial implications for the development of NK-based immunotherapeutics. This review will highlight the current knowledge of NK cell plasticity pertaining to the tumor microenvironment. Additionally, this review will pose critical and relevant questions that need to be addressed by the field in coming years.

show abstract

“…In general, there is no uniform evidence that the above-mentioned immunotherapeutic approaches benefit clinical outcomes in patients; and there is no consensus on the role of uNK cells in RM or RIF ( 180 ). However, recent studies have shown that uNK cells have special physiological functions in reproduction, especially in the establishment and maintenance of pregnancy ( 182 , 183 ), and corticosteroids/intralipid therapy that suppress NK cells activity may exacerbate pregnancy failure ( 184 , 185 ). Additionally, the state of the endometrium or the risk of pregnancy disease may be predicted by the examination of uNK cells in menstrual blood ( 25 ).…”

Section: Potential Of Unk Cells In Treating Reproductive Diseasesmentioning

confidence: 99%

Uterine Natural Killer Cells: A Rising Star in Human Pregnancy Regulation

Xie

Meng

et al. 2022

Front. Immunol.

View full text Add to dashboard Cite

Uterine natural killer (uNK) cells are an immune subset located in the uterus. uNK cells have distinct tissue-specific characteristics compared to their counterparts in peripheral blood and lymphoid organs. Based on their location and the pregnancy status of the host, uNK cells are classified as endometrial NK (eNK) cells or decidua NK (dNK) cells. uNK cells are important in protecting the host from pathogen invasion and contribute to a series of physiological processes that affect successful pregnancy, including uterine spiral artery remodeling, fetal development, and immunity tolerance. Abnormal alterations in uNK cell numbers and/or impaired function may cause pregnancy complications, such as recurrent miscarriage, preeclampsia, or even infertility. In this review, we introduce recent advances in human uNK cell research under normal physiological or pathological conditions, and summarize their unique influences on the process of pregnancy complications or uterine diseases. Finally, we propose the potential clinical use of uNK cells as a novel cellular immunotherapeutic approach for reproductive disorders.

show abstract

Role of Decidual Natural Killer Cells in Human Pregnancy and Related Pregnancy Complications

Cited by 90 publications

References 153 publications

Characterization of Epigenetic and Molecular Factors in Endometrium of Females with Infertility

Characterization of Epigenetic and Molecular Factors in Endometrium of Females with Infertility

Plasticity of NK cells in Cancer

Uterine Natural Killer Cells: A Rising Star in Human Pregnancy Regulation

Contact Info

Product

Resources

About