Decreased maternal serum acetate and impaired fetal thymic and regulatory T cell development in preeclampsia

Mingjing Hu, David Eviston, Peter Hsu, Eliana Mariño, Ann Chidgey, Brigitte Santner-Nanan, Kahlia Wong, James L. Richards, Yu Anne Yap, Fiona Collier, Ann Quinton, Steven Joung, Michael Peek, Ron Benzie, Laurence Macia, David Wilson, Ann Louise Ponsonby, Mimi L.K. Tang, Martin O’Hely, Norelle L. DalyCharles R. Mackay, Jane E. Dahlstrom, The BIS Investigator Group, Peter Vuillermin, Ralph Nanan

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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.

Original languageEnglish
Article number3031
Number of pages13
JournalNature Communications
Issue number1
Publication statusPublished - 10 Jul 2019


  • CD4-positive T cells
  • translational research

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