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). We explore how uNK cell dysfunction contributes to pregnancy complications, including preeclampsia, recurrent pregnancy loss, and placenta accreta spectrum (PAS) disorders, emphasizing their roles in immune tolerance and placental health. By detailing the distinct cytokine signaling pathways and functional subtypes of uNK cells, this review provides insights into their regulatory mechanisms essential for pregnancy maintenance. Additionally, we discuss emerging therapeutic strategies targeting uNK-trophoblast interactions and propose future research directions, including the development of non-invasive biomarkers and personalized interventions. This comprehensive review addresses critical knowledge gaps, aiming to advance research in reproductive immunology and guide therapeutic innovations in maternal health.
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| http://dx.doi.org/10.1016/j.cytogfr.2024.11.007 | DOI Listing |
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Expression of NKp46 and other activating inhibitory receptors on uterine endometrial NK cells in females with various reproductive failures: A review.
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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.
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Impact of antiphospholipid syndrome on placenta and uterine NK cell function: insights from a mouse model.
Sci Rep
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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.
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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.
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Curr Opin Allergy Clin Immunol
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