vuillermin-decreasedmaternal-2019.pdf (6.85 MB)
Decreased maternal serum acetate and impaired fetal thymic and regulatory T cell development in preeclampsia
journal contribution
posted on 2019-01-01, 00:00 authored by M Hu, D Eviston, P Hsu, E Mariño, A Chidgey, B Santner-Nanan, K Wong, J L Richards, Y A Yap, Fiona Collier, A Quinton, S Joung, M Peek, R Benzie, L Macia, D Wilson, A L Ponsonby, M L K Tang, M O’Hely, N L Daly, C R Mackay, J E Dahlstrom, R Saffery, K J Allen, S Ranganathan, D Burgner, L C Harrison, P Sly, T Dwyer, Peter VuillerminPeter Vuillermin, R NananMaternal 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.
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Journal
Nature communicationsVolume
10Article number
3031Pagination
1 - 13Publisher
Nature Publishing GroupLocation
London, Eng.Publisher DOI
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2041-1723Language
engPublication classification
C1 Refereed article in a scholarly journalCopyright notice
2019, The Author(s)Usage metrics
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