Antiphospholipid syndrome (APS) is a systemic autoimmune condition characterized by the persistent presence of antiphospholipid antibodies (aPL), and is commonly associated with thrombosis and pregnancy-related complications. To date, relatively little is known about the potential of NK cells in mediating the pathological effects of APS. While the role of NK cells in controlling immune responses and maintaining tissue homeostasis is relatively clear, the fact that they are also linked to various autoimmune conditions is now being highlighted. Given the impact of NK cells on immune regulation, vascular function, and pregnancy outcomes, the unifying message of a critical role for NK cells in APS emerges. As innate immune cells, NK cells might be activated in an antibody dependent manner and exert antibody-dependent cellular cytotoxicity (ADCC). In this process, NK cells recognize and bind to the Fc portion of antibodies that have attached to target cells. With their immunoregulatory properties in the uterus, NK cells play a crucial role in facilitating endometrial tissue remodeling, supporting vascular function, and contributing to placental formation, all of which are essential for a successful pregnancy. In APS, the presence of aPL may disrupt the delicate balance of NK cell-mediated immune regulation leading to alterations in cell activation, cytokine production, and cytotoxic functions. Given the multifactorial nature of NK cells in peripheral blood and uterus, the review provides insight into the potential underlying mechanisms through which NK cells may contribute to thrombosis and pregnancy complications in APS.

• Keywords
• NK cells, antiphospholipid antibodies, antiphospholipid syndrome, peripheral blood, placenta,
• MeSH
• Antibodies, Antiphospholipid immunology   MeSH
• Antiphospholipid Syndrome * immunology   metabolism   MeSH
• Antibody-Dependent Cell Cytotoxicity MeSH
• Killer Cells, Natural * immunology   metabolism   MeSH
• Pregnancy Complications immunology   MeSH
• Humans MeSH
• Pregnancy MeSH
• Thrombosis immunology   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Pregnancy MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Antibodies, Antiphospholipid MeSH

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. Analyses of APS placentas showed a reduced cell proliferation, lower protein content and thinning of endothelial cells. Disturbances in APS trophoblast cells were linked to a cell cycle shift in cytotrophoblast cells, and a reduced number of spiral artery-associated trophoblast giant cells (SpA-TGC). Transcriptomic profiling of placental tissue highlighted disruptions in cell cycle regulation with notable downregulation of genes involved in developmental or signaling processes. Cellular senescence, metabolic and p53-related pathways were also enriched, suggesting potential mechanisms underlying placental dysfunction in APS. Thrombotic events, though occasionally detected, appeared to have no significant impact on the overall pathological changes. The increased number of dysfunctional uNK cells was not associated with enhanced cytotoxic capabilities. Transcriptomic data corroborated these findings, showing prominent suppression of NK cell secretory capacity and cytokine signaling pathways. Our study highlights the multifactorial nature of APS-associated placental pathologies, which involve disrupted angiogenesis, cell cycle regulation, and NK cell functionality.

• Keywords
• Anti-β2GPI antibodies, Antiphospholipid syndrome, Cell proliferation, Endothelial cells, Mouse model, NK cells, Placenta, RNAseq, Trophoblasts,
• MeSH
• Antiphospholipid Syndrome * immunology   pathology   MeSH
• Killer Cells, Natural * immunology   metabolism   MeSH
• Disease Models, Animal * MeSH
• Mice MeSH
• Placenta * metabolism   pathology   MeSH
• Cell Proliferation MeSH
• Gene Expression Profiling MeSH
• Pregnancy MeSH
• Transcriptome MeSH
• Trophoblasts metabolism   pathology   immunology   MeSH
• Uterus * pathology   metabolism   MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Pregnancy MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH