Format

Send to

Choose Destination
Nat Commun. 2019 Jul 10;10(1):3031. doi: 10.1038/s41467-019-10703-1.

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

Author information

1
Charles Perkins Centre Nepean, The University of Sydney, Penrith, 2750, NSW, Australia.
2
Sydney Medical School Nepean, The University of Sydney, Penrith, 2750, NSW, Australia.
3
Discipline of Paediatrics and Child Health, Sydney Medical School, The University of Sydney, Sydney, 2006, NSW, Australia.
4
Department of Allergy and Immunology, The Children's Hospital at Westmead, Sydney, 2145, NSW, Australia.
5
Infection and Immunity Program, Biomedicine Discovery Institute, Monash University, Clayton, 3800, VIC, Australia.
6
Department of Anatomy and Developmental Biology, Biomedicine Discovery Institute, Monash University, Clayton, 3800, VIC, Australia.
7
Deakin University, Geelong, 3220, VIC, Australia.
8
Barwon Health, Geelong, 3220, VIC, Australia.
9
Murdoch Children's Research Institute, Parkville, 3052, VIC, Australia.
10
School of Health, Medical and Applied Science, Central Queensland University, Sydney, 2000, NSW, Australia.
11
Nepean Hospital, Penrith, 2750, NSW, Australia.
12
ANU Medical School, College of Health and Medicine, The Australian National University, Canberra, 0200, ACT, Australia.
13
Discipline of Obstetrics, Gynaecology and Neonatology, Sydney Medical School Nepean, The University of Sydney, Penrith, 2750, NSW, Australia.
14
Department of Pathology, School of Medical Sciences, Charles Perkins Centre, The University of Sydney, Sydney, 2006, NSW, Australia.
15
Centre for Molecular Therapeutics, AITHM, James Cook University, Cairns, 4814, QLD, Australia.
16
National Centre for Epidemiology and Population Health, Research School of Population Health, College of Health and Medicine, The Australian National University, Canberra, 0200, ACT, Australia.
17
The Royal Children's Hospital, Parkville, Melbourne, 3052, VIC, Australia.
18
Department of Paediatrics, University of Melbourne, Melbourne, 3010, VIC, Australia.
19
Anatomical Pathology, ACT Pathology, Canberra Hospital and ANU Medical School, College of Health and Medicine, The Australian National University, Canberra, 0200, ACT, Australia.
20
Centre for Food and Allergy Research, Parkville, 3052, VIC, Australia.
21
Charles Perkins Centre Nepean, The University of Sydney, Penrith, 2750, NSW, Australia. ralph.nanan@sydney.edu.au.
22
Sydney Medical School Nepean, The University of Sydney, Penrith, 2750, NSW, Australia. ralph.nanan@sydney.edu.au.

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.

PMID:
31292453
DOI:
10.1038/s41467-019-10703-1

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center