ArticleFrontiers in immunology2021
Expression of Immune Checkpoint Receptors in Placentae With Infectious and Non-Infectious Chronic Villitis.
Article in Frontiers in immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 14 citations in OpenAlex.
- Recent insights into the immunobiology of congenital cytomegalovirus infection.Current opinion in physiology · 2026Article
- Pan-viral metagenomic sequencing demonstrates that cryptic viral infection is rarely observed in villitis of unknown etiology.Placenta · 2025Article
- Immune surveillance of cytomegalovirus in tissues.Cellular & molecular immunology · 2024Review
- Effect of Anti-TNF Biologic Exposure During Pregnancy on Villitis of Unknown Etiology Diagnoses in Patients with Autoimmune Disease.Reproductive sciences (Thousand Oaks, Calif.) · 2024Article
- Spatial proteomics reveals phenotypic and functional differences in T cell and macrophage subsets during villitis of unknown etiology.Scientific reports · 2024Article
- Immunosequencing and Profiling of T Cells at the Maternal-Fetal Interface of Women with Preterm Labor and Chronic Chorioamnionitis.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- Spatial profiling of the placental chorioamniotic membranes reveals upregulation of immune checkpoint proteins during Group BFrontiers in cellular and infection microbiology · 2023Article
- SARS-CoV-2 Infection in Pregnancy: Placental Histomorphological Patterns, Disease Severity and Perinatal Outcomes.International journal of environmental research and public health · 2022Article
- Chronic Inflammatory Placental Disorders Associated With Recurrent Adverse Pregnancy Outcome.Frontiers in immunology · 2022Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Pregnancy is an immunological paradox whereby maternal immunity accepts a genetically unique fetus (or fetuses), while maintaining protective innate and adaptive responses to infectious pathogens. This close contact between the genetically diverse mother and fetus requires numerous mechanisms of immune tolerance initiated by trophoblast cell signals. However, in a placental condition known as villitis of unknown etiology (VUE), there appears to be a breakdown in this tolerance allowing maternal cytotoxic T-cells to traffic into the placenta to destroy fetal villi. VUE is associated with several gestational complications and an increased risk of recurrence in a subsequent pregnancy, making it a significant obstetrical diagnosis. The cause of VUE remains unclear, but dysfunctional signaling through immune checkpoint pathways, which have a critical role in blunting immune responses, may play an important role. Therefore, using placental tissue from normal pregnancy (n=8), VUE (n=8) and cytomegalovirus (CMV) infected placentae (n=4), we aimed to identify differences in programmed cell death 1 (PD-1), programmed death ligand-1 (PD-L1), LAG3 and CTLA4 expression between these etiologies by immunohistochemistry (IHC). Results demonstrated significantly lower expression of PD-L1 on trophoblast cells from VUE placentae compared to control and CMV infection. Additionally, we observed significantly higher counts of PD-1+ (>100 cells/image) and LAG3+ (0-120 cells/image) cells infiltrating into the villi during VUE compared to infection and control. Minimal CTLA4 staining was observed in all placentae, with only a few Hofbauer cells staining positive. Together, this suggests that a loss of tolerance through immune checkpoint signaling may be an important mechanism leading to the activation and trafficking of maternal cells into fetal villi during VUE. Further mechanistic studies are warranted to understand possible allograft rejection more clearly and in developing effective strategies to prevent this condition from occurring
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