Journal article
Decreased maternal serum acetate and impaired fetal thymic and regulatory T cell development in preeclampsia
M Hu, D Eviston, P Hsu, E Mariño, A Chidgey, B Santner-Nanan, K Wong, JL Richards, YA Yap, F Collier, A Quinton, S Joung, M Peek, R Benzie, L Macia, D Wilson, AL Ponsonby, MLK Tang, M O’Hely, NL Daly Show all
Nature Communications | NATURE PORTFOLIO | Published : 2019
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 cont..
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Awarded by Australian Research Council
Funding Acknowledgements
We would like to thank Dr. Tobin Northfield for assistance with the data processing. Appreciation is also extended to participants of the Barwon Infant Study and the participants of the Nepean Cohort 1-4. We would also like to thank Mrs Amanda Bullman Chief Scientist in Charge of Immunohistochemistry, Anatomical Pathology, ACT Pathology, Canberra Hospital who performed the immunohistochemical studies. We also thank Susan Abuckle and Nicky Graf for providing thymus and spleen specimens from the Children's Hospital Westmead. Drs Michael Conlon and David Topping, Commonwealth Scientific, and Industrial Research Organization, Adelaide, who measured the serum acetate levels in the BIS cohort. We are grateful to the Australian Women and Children's Research Foundation and the Nepean Medical Research Fund for supporting this project. The James Cook University NMR facility was partially funded by the Australian Research Council (LE120100015, LE160100218).