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

Mingjing Hu, David Eviston, Peter Hsu, Eliana Mariño, Ann Chidgey, Brigitte Santner-Nanan, Kahlia Wong, James L. Richards, Yu Anne Yap, Fiona Collier, Ann Quinton, Steven Joung, Michael Peek, Ron Benzie, Laurence Macia, David Wilson, Ann Louise Ponsonby, Mimi L.K. Tang, Martin O’Hely, Norelle L. Daly & 5 others Charles R. Mackay, Jane E. Dahlstrom, The BIS Investigator Group, Peter Vuillermin, Ralph Nanan

Research output: Contribution to journalArticleResearchpeer-review

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.

Original languageEnglish
Article number3031
Number of pages13
JournalNature Communications
Volume10
Issue number1
DOIs
Publication statusPublished - 10 Jul 2019

Keywords

  • CD4-positive T cells
  • translational research

Cite this

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 ; Nanan, Ralph. / Decreased maternal serum acetate and impaired fetal thymic and regulatory T cell development in preeclampsia. In: Nature Communications. 2019 ; Vol. 10, No. 1.
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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.",
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author = "Mingjing Hu and David Eviston and Peter Hsu and Eliana Mari{\~n}o and Ann Chidgey and Brigitte Santner-Nanan and Kahlia Wong and Richards, {James L.} and Yap, {Yu Anne} and Fiona Collier and Ann Quinton and Steven Joung and Michael Peek and Ron Benzie and Laurence Macia and David Wilson and Ponsonby, {Ann Louise} and Tang, {Mimi L.K.} and Martin O’Hely and Daly, {Norelle L.} and Mackay, {Charles R.} and Dahlstrom, {Jane E.} and {The BIS Investigator Group} and David Burgner and Peter Vuillermin and Ralph Nanan",
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Hu, M, Eviston, D, Hsu, P, Mariño, E, Chidgey, A, Santner-Nanan, B, Wong, K, Richards, JL, Yap, YA, Collier, F, Quinton, A, Joung, S, Peek, M, Benzie, R, Macia, L, Wilson, D, Ponsonby, AL, Tang, MLK, O’Hely, M, Daly, NL, Mackay, CR, Dahlstrom, JE, The BIS Investigator Group, Vuillermin, P & Nanan, R 2019, 'Decreased maternal serum acetate and impaired fetal thymic and regulatory T cell development in preeclampsia', Nature Communications, vol. 10, no. 1, 3031. https://doi.org/10.1038/s41467-019-10703-1

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; Nanan, Ralph.

In: Nature Communications, Vol. 10, No. 1, 3031, 10.07.2019.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Santner-Nanan, Brigitte

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AU - Benzie, Ron

AU - Macia, Laurence

AU - Wilson, David

AU - Ponsonby, Ann Louise

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AU - Daly, Norelle L.

AU - Mackay, Charles R.

AU - Dahlstrom, Jane E.

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AU - Burgner, David

AU - Vuillermin, Peter

AU - Nanan, Ralph

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