The presence of granulated lymphocytes in the human uterine mucosa, known as decidua during pregnancy, or endometrium otherwise, was first noted in the nineteenth century, but it was not until 1990 that these cells were identified as a type of natural killer (NK) cell. From the outset, uterine NK (uNK) cells were found to be less cytotoxic than their circulating counterparts, peripheral NK (pNK) cells. Recently, unbiased approaches have defined three subpopulations of uNK cells, all of which cluster separately from pNK cells. Here, we review the history of research into uNK cells, including their ability to interact with placental extravillous trophoblast cells and their potential role in regulating placental implantation. We go on to review more recent advances that focus on uNK cell development and heterogeneity and their potential to defend against infection and to mediate memory effects. Finally, we consider how a better understanding of these cells could be leveraged in the future to improve outcomes of pregnancy for mothers and babies.
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http://dx.doi.org/10.1146/annurev-immunol-102119-075119 | DOI Listing |
Reprod Med Biol
January 2025
Department of Obstetrics and Gynecology School of Medicine, Hyogo Medical University Nishinomiya Hyogo Japan.
Background: Uterine endometrial natural killer (uNK) cells represent major leukocytes in the mid-secretory phase of the cell cycle, and their number is further increased during early pregnancy. The activating and inhibitory receptors expressed on their surface mediate various functions of uNK cells, such as cytotoxicity, cytokine production, spiral artery remodeling, and self-recognition.
Methods: This study reviewed the most recent information (PubMed database, 175 articles included) regarding the activating and inhibitory receptors on uNK cells in human females with healthy pregnancies and the evidence indicating their significance in various reproductive failures.
Sci Rep
December 2024
Laboratory of Molecular and Cellular Immunology, Institute of Molecular Biology NAS RA, 7 Hasratyan Str., Yerevan, 0014, Armenia.
Antiphospholipid syndrome (APS) is associated with recurrent pregnancy morbidity, yet the underlying mechanisms remain elusive. We performed multifaceted characterization of the biological and transcriptomic signatures of mouse placenta and uterine natural killer (uNK) cells in APS. Histological analysis of APS placentas unveiled placental abnormalities, including disturbed angiogenesis, occasional necrotic areas, fibrin deposition, and nucleated red blood cell enrichment.
View Article and Find Full Text PDFMucosal Immunol
December 2024
Microbiology and Immunology Department, Loyola University Health Science Campus, Maywood, IL, United States 60153. Electronic address:
The murine uterus contains three subsets of innate lymphoid cells (ILCs). Innate lymphoid cell type 1 (ILC1) and conventional natural killer (cNK) cells seed the uterus before puberty. Tissue-resident NK (trNK) cells emerge at puberty and vary in number during the estrous cycle.
View Article and Find Full Text PDFJCI Insight
December 2024
Robinson Research Institute and School of Biomedicine, The University of Adelaide, Adelaide, South Australia, Australia.
Curr Opin Allergy Clin Immunol
February 2025
Department of Medicine and Medical Specialties, A. Cardarelli Hospital, Naples, Italy.
Purpose Of Review: We aim to explore the most recent insights into the pathogenesis of recurrent angioedema caused by different mechanisms and then focus on the management and treatment approaches available.
Recent Findings: The recently developed DANCE consensus classification identifies five types of angioedema: mast cell-mediated (AE-MC), bradykinin-mediated, because of intrinsic vascular endothelium dysfunction (AE-VE), drug-induced (AE-DI), and due to unknown mechanisms (AE-UNK). These subtypes require different management with treatment choices targeting the main pathogenetic pathways involved in each form.
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