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

• Published in: Nature communications Vol. 10; no. 1; pp. 3031 - 13
• Main Authors: 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., Vuillermin, Peter, Nanan, Ralph
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 10.07.2019; Nature Publishing Group; Nature Portfolio
• Subjects: 13/31; 13/51; 14/34; 140/131; 631/250/1619/554/1898; 64/60; 692/308/575; Acetates - administration & dosage; Acetates - blood; Acetates - immunology; Acetates - metabolism; Acetic acid; Adult; AIRE Protein; Animals; Animals, Newborn; Atopy; Case-Control Studies; CD4 antigen; Child Development; Child, Preschool; Dietary Supplements; Fatty acids; Female; Fetus - cytology; Fetus - diagnostic imaging; Fetus - immunology; Fetuses; Gastrointestinal Microbiome - immunology; Germ-Free Life - immunology; Germfree; Humanities and Social Sciences; Humans; Immune Tolerance - immunology; Infant; Infant, Newborn; Intestine; Longitudinal Studies; Lymphocytes; Lymphocytes T; Maternal-Fetal Exchange - immunology; Mice; multidisciplinary; Offspring; Organ Size - immunology; Pathogenesis; Pre-eclampsia; Pre-Eclampsia - blood; Pre-Eclampsia - diagnosis; Pre-Eclampsia - immunology; Preeclampsia; Pregnancy; Prenatal Exposure Delayed Effects - immunology; Prenatal Exposure Delayed Effects - pathology; Prenatal Exposure Delayed Effects - prevention & control; Prospective Studies; Science; Science (multidisciplinary); Supplements; T-Lymphocytes, Regulatory - immunology; Thymus; Thymus Gland - cytology; Thymus Gland - diagnostic imaging; Thymus Gland - growth & development; Thymus Gland - immunology; Transcription Factors - immunology; Transcription Factors - metabolism; Ultrasonography, Prenatal; Young Adult
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-019-10703-1

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. Maternal immunological dysregulation might affect the immunological development of the fetus. Here the authors show that decreased maternal acetate is associated with preeclampsia, impaired fetal thymic output and regulatory T cell development.