Decreased maternal serum acetate and impaired fetal thymic and regulatory T cell development in preeclampsia.
Mingjing HuDavid EvistonPeter HsuEliana MariñoAnn ChidgeyBrigitte Santner-NananKahlia WongJames L RichardsYu Anne YapFiona CollierAnn E QuintonSteven JoungMichael J PeekRon BenzieLaurence MaciaDavid WilsonAnn-Louise PonsonbyMimi L K TangMartin O'HelyNorelle L DalyCharles R MackayJane E Dahlstromnull nullPeter VuillerminRalph NananPublished in: Nature communications (2019)
Maternal immune dysregulation seems to affect fetal or postnatal immune development. Preeclampsia is a pregnancy-associated disorder with an immune basis and is linked to atopic disorders in offspring. Here we show reduction of fetal thymic size, altered thymic architecture and reduced fetal thymic regulatory T (Treg) cell output in preeclamptic pregnancies, which persists up to 4 years of age in human offspring. In germ-free mice, fetal thymic CD4+ T cell and Treg cell development are compromised, but rescued by maternal supplementation with the intestinal bacterial metabolite short chain fatty acid (SCFA) acetate, which induces upregulation of the autoimmune regulator (AIRE), known to contribute to Treg cell generation. In our human cohorts, low maternal serum acetate is associated with subsequent preeclampsia, and correlates with serum acetate in the fetus. These findings suggest a potential role of acetate in the pathogenesis of preeclampsia and immune development in offspring.
Keyphrases
- pregnancy outcomes
- early onset
- single cell
- birth weight
- endothelial cells
- pregnant women
- cell therapy
- high fat diet
- transcription factor
- fatty acid
- type diabetes
- preterm infants
- cell proliferation
- preterm birth
- multiple sclerosis
- adipose tissue
- induced pluripotent stem cells
- insulin resistance
- signaling pathway
- physical activity
- pluripotent stem cells
- skeletal muscle
- risk assessment
- high fat diet induced