ArticleJournal of immunology (Baltimore, Md. : 1950)2016
Lipopolysaccharide-Induced Chorioamnionitis Promotes IL-1-Dependent Inflammatory FOXP3+ CD4+ T Cells in the Fetal Rhesus Macaque.
Article in Journal of immunology (Baltimore, Md. : 1950), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 61 citations in OpenAlex.
- Cellular immune responses in amniotic fluid of women with preterm labor and intra-amniotic infection or intra-amniotic inflammation.American journal of reproductive immunology (New York, N.Y. : 1989) · 2019Trial
- Fetal T Cell Activation in the Amniotic Cavity during Preterm Labor: A Potential Mechanism for a Subset of Idiopathic Preterm Birth.Journal of immunology (Baltimore, Md. : 1950) · 2019Trial
- Effector and Activated T Cells Induce Preterm Labor and Birth That Is Prevented by Treatment with Progesterone.Journal of immunology (Baltimore, Md. : 1950) · 2019Trial
- Reconceptualizing chorioamnionitis as an immune-mediated inflammatory disorder at the maternal-fetal interface.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- The placenta as a window into neonatal brain injury.Seminars in perinatology · 2025Review
- Single-cell analysis of the decidua unveils the mechanism of anti-inflammatory exosomes for chorioamnionitis in nonhuman primates.Science advances · 2025Article
- Systemic inflammatory responses to repeated and increasing endotoxin challenges in fetal sheep.Physiological reports · 2025Article
- Reduced IL-17A levels in neonates born to mothers with diabetes mellitus or infection during pregnancy.Frontiers in pediatrics · 2025Article
- Chorioamnionitis accelerates granule cell and oligodendrocyte maturation in the cerebellum of preterm nonhuman primates.Journal of neuroinflammation · 2024Article
- The eNAMPT/TLR4 inflammatory cascade drives the severity of intra-amniotic inflammation in pregnancy and predicts infant outcomes.Frontiers in physiology · 2023Article
- The role of interleukin-1 in perinatal inflammation and its impact on transitional circulation.Frontiers in pediatrics · 2023Review
- Aberrant newborn T cell and microbiota developmental trajectories predict respiratory compromise during infancy.iScience · 2022Article
- Differential Brain and Cerebrospinal Fluid Proteomic Responses to Acute Prenatal Endotoxin Exposure.Molecular neurobiology · 2022Article
- Review
- HSP70: an alarmin that does not induce high rates of preterm birth but does cause adverse neonatal outcomes.The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians · 2021Article
- Lung development and immune status under chronic LPS exposure in rat pups with and without CD26/DPP4 deficiency.Cell and tissue research · 2021Article
- The Distinct Immune Nature of the Fetal Inflammatory Response Syndrome Type I and Type II.ImmunoHorizons · 2021Article
- Article
- Prenatal inflammation enhances antenatal corticosteroid-induced fetal lung maturation.JCI insight · 2020Article
- A Broad Spectrum Chemokine Inhibitor Prevents Preterm Labor but Not Microbial Invasion of the Amniotic Cavity or Neonatal Morbidity in a Non-human Primate Model.Frontiers in immunology · 2020Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Chorioamnionitis is associated with preterm labor and fetal inflammatory response syndrome (FIRS), causing fetal organ injury and morbidity, particularly in extremely premature infants. However, the effects of inflammation on the fetal immune system remain poorly understood, due to the difficulty of studying immune development in infants. Therefore, we used the model of intra-amniotic LPS administered at ∼80% gestation in rhesus monkeys to cause chorioamnionitis and FIRS that is similar in human pathology. Importantly, the frequency of IL-17(+) and IL-22(+) CD4(+) T cells increased in the spleen of LPS-exposed fetuses, whereas regulatory T cell (Treg) frequency decreased. These changes persisted for at least 48 h. Notably, Th17 cytokines were predominantly expressed by FOXP3(+)CD4(+) T cells and not by their FOXP3(-) counterparts. Bifunctional IL-17(+)FOXP3(+) exhibited a phenotype of inflammatory Tregs (RORc(High/+), Helios(Low/-), IL-2(+), IFN-γ(+), and IL-8(+)) compared with typical FOXP3(+) cells. Diminished splenic Treg frequency in LPS-exposed fetuses was associated with inadequate Treg generation in the thymus. Mechanistically, the emergence of inflammatory Tregs was largely dependent on IL-1 signaling. However, blockage of IL-1R signaling did not abolish the deleterious effects of LPS on Treg frequency in the thymus or spleen. Collectively, we demonstrate that a prenatal inflammatory environment leads to inadequate Treg generation in the thymus with a switch of splenic Tregs toward an inflammatory phenotype. Both processes likely contribute to the pathogenesis of chorioamnionitis. Approaches to manipulate Treg numbers and function could thus be useful therapeutically to alleviate FIRS in preterm infants.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.