Decidual natural killer (dNK) cells are believed to be critical for maintaining maternal/fetal tolerance and regulating placental vascular remodeling based upon their abundance and unique phenotype during early pregnancy. However, the mechanism for how the dNK cells play such important roles in successful pregnancy remains undefined. Here, we identified a subtype of dNK cells characterized as having a CD3(-)CD56(bright)CD25(+) phenotype. We found that CD56(bright)CD25(+) NK cells preferentially localize to the maternal/fetal interface during early human pregnancy. CD25(+) dNK cells account for approximately 75% of CD25-expressing decidual immune cells (DICs). However, less than 5% of CD25-positive peripheral blood mononuclear cells are CD25(+) NK cells. Furthermore, CD25(+) and CD25(-) dNK cells exhibit distinct phenotypes: CD25(+) dNK cells display a more activated phenotype and greater cytokine-secreting capacity. Interestingly, coculture of peripheral NK (pNK) cells with primary trophoblasts upregulates the percentage of CD25-expressing pNK cells, resulting in increased expression of activation markers and cytokine production by pNK cells. In addition, we demonstrated that the CXCL12/CXCR4 axis is crucial for the recruitment of CD25(+) dNK cells and contributes to the accumulation of CD3(-)CD56(bright)CD25(+) dNK cells at the maternal/fetal interface. Thus, our data reveal that the crosstalk between trophoblasts and pNK cells leads to the accumulation of CD3(-)CD56(bright)CD25(+) dNK cells, which exert a regulating effect at the maternal/fetal interface.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4654367 | PMC |
http://dx.doi.org/10.1038/cmi.2014.26 | 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.
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!