Background: The role of decidual natural killer (dNK) cells in normal and complicated pregnancy and their relation with peripheral NK (pNK) cells remains unclear. The study aim was phenotypic analysis of pNK and dNK cells at time of miscarriage in recurrent spontaneous miscarriage (RSM) patients to assess whether measuring levels of pNK cell populations can reflect changes in dNK cells or not.
Methods: This study included 40 middle aged pregnant women in the 1st trimester subjected to evacuation because of a current miscarriage. They had a history of previous ≥ two unexplained miscarriages. Frequencies of pNK and dNK cells, based on the expression of CD56, CD16, inhibitory (CD158b) and activating (CD161) Killer immunoglobulin-like receptors (KIRs), were detected by flow cytometry.
Results: Percentages of CD56 NK cells in peripheral blood and decidua were 17.5 % and 17.3 %, respectively. In both blood and decidua, CD56 NK cells were exceeding CD56 NK cells. The CD56 CD16 NK cells were the predominating subset of NK cells, followed by CD56 CD16. No substantial differences were detected in the levels of KIRs expression by the different NK subsets between blood and decidua. Abnormal up-regulation of both CD161 and CD158b on NK cells was observed in blood and decidua.
Conclusion: At the time of miscarriage, patients with RSM have an extremely active immune system and an increased number of toxic NK cells both in blood and decidua. The pNK cells reflect dNK cell changes during miscarriage and may be a useful non-invasive predicting tool in reproductive failure setting.
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http://dx.doi.org/10.1016/j.jri.2020.103130 | DOI Listing |
Am J Reprod Immunol
January 2025
Department of Obstetrics and Gynecology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.
Preeclampsia is one of the most severe obstetric complications, yet its pathogenesis remains unclear. Decidual natural killer (dNK) cells, the most abundant immune cells at the maternal-fetal interface, are closely associated with preeclampsia due to abnormalities in their quantity, phenotype, and function. This review summarizes the molecular mechanisms by which dNK cells regulate extravillous trophoblast (EVT) invasion, promote uterine spiral artery remodeling, and maintain immune tolerance.
View Article and Find Full Text PDFMol Cell Biochem
December 2024
Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Qilu Hospital of Shandong University, No.44 Wenhua Xi Road, Jinan, 250012, Shandong, China.
In patients with recurrent pregnancy loss (RPL), excessive activation of decidual natural killer (dNK) cells has been widely observed, yet the precise underlying mechanisms remain to be elucidated. We collected decidual specimens from RPL patients and controls to assess GRIM19 expression, activation phenotype, cytotoxic function, inflammatory cytokine secretion, and mitochondrial homeostasis in dNK cells. Furthermore, we established a GRIM19-knockout NK-92MI cell line and a GRIM19 ± C57BL/6J mouse model to investigate the relationship between GRIM19 downregulation and dNK immune dysregulation, ultimately contributing to pregnancy loss.
View Article and Find Full Text PDFMol Hum Reprod
November 2024
Shenzhen Key Laboratory of Reproductive Immunology for Peri-Implantation, Shenzhen Zhongshan Institute for Reproductive Medicine and Genetics, Shenzhen Zhongshan Obstetrics & Gynecology Hospital (formerly Shenzhen Zhongshan Urology Hospital), Shenzhen, China.
Natural killer (NK) cells are the most abundant leukocytes located at the maternal-fetal interface; they respond to pregnancy-related hormones and play a pivotal role in maintaining the homeostatic micro-environment during pregnancy. However, due to the high heterogeneity of NK cell subsets, their categorization has been controversial. Here, we review previous studies on uterine NK cell subsets, including the classic categorization based on surface markers, functional molecules, and developmental stages, as well as single-cell RNA sequencing-based clustering approaches.
View Article and Find Full Text PDFInt J Med Sci
November 2024
Center of Translational Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, 610041, China.
EMBO J
November 2024
Department of Reproductive Immunology, The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200030, People's Republic of China.
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