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

Hu, Mingjing, Eviston, David, Hsu, Peter, Mariño, Eliana, Chidgey, Ann, Santner-Nanan, Brigitte, Wong, Kahlia, Richards, James L., Yap, Yu Anne, Collier, Fiona, Quinton, Ann, Joung, Steven, Peek, Michael, Benzie, Ron, Macia, Laurence, Wilson, David, Ponsonby, Ann-Louise, Tang, Mimi L. K., O'Hely, Martin, Daly, Norelle L., Mackay, Charles R., Dahlstrom, Jane E., The BIS Investigator Group, , Vuillermin, Peter, and Nanan, Ralph (2019) Decreased maternal serum acetate and impaired fetal thymic and regulatory T cell development in preeclampsia. Nature Communications, 10. 3031.

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Abstract

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.

Item ID: 60084
Item Type: Article (Research - C1)
ISSN: 2041-1723
Copyright Information: © The Author(s) 2019. Open Access: this article is licensed under a Creative Commons Attribution 4.0 International License.
Funders: Australian Women and Children's Research Foundation (OZWAC), Nepean Medical Research Fund, Australian Research Council (ARC)
Projects and Grants: ARC LEI 20100015, LE160100218
Date Deposited: 31 Jul 2019 07:39
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1101 Medical Biochemistry and Metabolomics > 110101 Medical Biochemistry: Amino Acids and Metabolites @ 100%
SEO Codes: 97 EXPANDING KNOWLEDGE > 970106 Expanding Knowledge in the Biological Sciences @ 100%
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