Problem: Pyruvate dehydrogenase kinase 1 (PDK1) is an important enzyme for immune cell development. However, PDK1's role in human decidual natural killer (dNK) cells remains largely unknown.
Methods Of Study: PDK1 expression in dNK cells from patients with recurrent spontaneous abortions (RSA) and age-matched healthy controls was analyzed by qRT-PCR, western bolt and flow cytometry. Moreover, dNK cells were treated with PDK1 inhibitor or the PDK1 siRNA followed by functional assays.
Results: The dNK cells from patients who underwent RSAs had higher mRNA expression and increased protein of PDK1, perforin (PRF1), Granzyme B (GZMB), IFN-γ (IFNG), and CD107a expression compared to dNK cells from age-matched healthy controls. Perforin, Granzyme B, IFN-γ and CD107a expression levels in dNK cells were down-regulated when dNK cells were treated with a PDK1 inhibitor. As measured by the Cr release assay, the killing activity of dNK cells was found to be decreased. We also demonstrated that PDK1 blockade could up-regulate the migration and adhesion of dNK cells. Furthermore, PDK1 inhibition reduced the glycolysis of dNK cells.
Conclusion: This study suggested that PDK1 plays an important role in regulating dNK cell functions and human RSA.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1111/aji.13765 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Role of Decidual Natural Killer Cells in the Pathogenesis of Preeclampsia.
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 PDFImmune dysregulation of decidual NK cells mediated by GRIM19 downregulation contributes to the occurrence of recurrent pregnancy loss.
Mol 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 PDFUnderstanding the heterogeneity of natural killer cells at the maternal-fetal interface: implications for pregnancy health and disease.
Mol 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 PDFAbnormal miR-122-5p expression in decidual NK cells and its impact on trophoblast behavior: insights into unexplained recurrent pregnancy loss.
Int 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.
Article Synopsis
- Early pregnancy features high levels of natural killer (NK) cells at the maternal-fetal interface, which are crucial for fetal development and remodeling uterine arteries.
- Aberrant activity of decidual NK (dNK) cells is linked to recurrent pregnancy loss (RPL), but the exact molecular mechanisms behind their function need more research.
- This study highlights that downregulation of miR-122-5p in dNK cells from RPL patients affects their function, suggesting that miR-122-5p may play a role in maintaining immune tolerance during pregnancy.
TNFSF14 natural killer cells prevent spontaneous abortion by restricting leucine-mediated decidual stromal cell senescence.
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.
Article Synopsis
- The endometrium transforms into a structure called decidua during pregnancy preparation, with senescent decidual stromal cells (DSCs) increasing but poorly understood mechanisms.
- Researchers used single-cell RNA transcriptomics to discover that higher levels of the BCAA transporter SLC3A2 accompany cell senescence in DSCs during decidualization.
- A high leucine diet contributes to increased DSC senescence and embryo loss in mice, while dNK cells can counteract this senescence through the TNFSF14/TNFRSF14 pathway, highlighting potential for therapeutic interventions in preventing pregnancy loss.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!