Uterine spiral artery remodeling is required for successful human pregnancy; impaired remodeling is associated with pregnancy complications, including late miscarriage, preeclampsia, and fetal growth restriction. The molecular triggers of remodeling are not known, but it is now clear that there are "trophoblast-independent" and "trophoblast-dependent" stages. Uterine natural killer (uNK) cells are abundant in decidualized endometrium in early pregnancy; they surround spiral arteries and secrete a range of angiogenic growth factors. We hypothesized that uNK cells mediate the initial stages of spiral artery remodeling. uNK cells and extravillous trophoblast (EVT) cells were isolated from early pregnancy decidua and placenta. Chorionic plate arteries from full-term placentas and spiral arteries from nonpregnant myometrium were cultured with angiogenic growth factors or conditioned medium (CM) from uNK cells or EVT or uNK cell/EVT cocultures. In both vessel models, uNK cell CM induced disruption of vascular smooth muscle cells (VSMCs) and breakdown of extracellular matrix components. Angiopoietin (Ang)-1, Ang-2, interferon-γ, and VEGF-C also disrupted VSMC integrity with an Ang-2 inhibitor abrogating the effect of uNK cell CM. These results provide compelling evidence that uNK cells contribute to the early stages of spiral artery remodeling; failure of this process could contribute to pregnancy pathology.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1096/fj.12-210310 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Impact of antiphospholipid syndrome on placenta and uterine NK cell function: insights from a mouse model.
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 PDFTissue-resident natural killer cells derived from conventional natural killer cells are regulated by progesterone in the uterus.
Mucosal 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 PDFRegulatory T cells promote decidual vascular remodeling and modulate uterine NK cells in pregnant mice.
JCI Insight
December 2024
Robinson Research Institute and School of Biomedicine, The University of Adelaide, Adelaide, Australia.
Article Synopsis
- Regulatory T (Treg) cells are crucial for maintaining immune tolerance during pregnancy, ensuring that the mother’s body accepts the developing fetus and placenta.
- In a study using a specific mouse model, researchers found that depleting Treg cells early in pregnancy led to problems with the remodeling of uterine arteries, reduced natural killer (uNK) cell numbers, and resulted in fetal loss and growth restriction.
- By transferring Treg cells from healthy donors, the negative effects on vascular function and fetal health were mitigated, highlighting the important role Treg cells play in adapting the uterine environment for a successful pregnancy and their connection to issues like preeclampsia.
Exploring the management of recurrent angioedema caused by different mechanisms.
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.
Cytokine modulation and immunoregulation of uterine NK cells in pregnancy disorders.
Cytokine Growth Factor Rev
November 2024
Department of Obstetrics, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266000, China. Electronic address:
Uterine natural killer (uNK) cells play a pivotal role in promoting placental development and supporting maternal-fetal immune tolerance, primarily through cytokine regulation and growth factor production. While the importance of uNK cells in pregnancy is well-established, the mechanisms of their interactions with trophoblasts and contributions to various pregnancy complications remain incompletely understood. This review highlights recent advancements in understanding uNK cell functions, with a focus on cytokine production, growth factor secretion, and receptor-ligand interactions, particularly involving killer immunoglobulin-like receptors (KIR) and human leukocyte antigen-C (HLA-C).
View Article and Find Full Text PDFWant 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!