ResearchIn-Press PreviewImmunologyReproductive biology Open Access | 10.1172/jci.insight.169836
1Robinson Research Institute and School of Biomedicine, The University of Adelaide, Adelaide, Australia
2Robinson Research Institute and School of Biomedicine, The University of Adelaide, Adelaide, United States of America
3Flinders Health and Medical Research Institute, Flinders University, Adelaide, Australia
4Women and Children’s Health Research Institute, Department of Obstetrics an, University of Alberta, Edmonton, Canada
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1Robinson Research Institute and School of Biomedicine, The University of Adelaide, Adelaide, Australia
2Robinson Research Institute and School of Biomedicine, The University of Adelaide, Adelaide, United States of America
3Flinders Health and Medical Research Institute, Flinders University, Adelaide, Australia
4Women and Children’s Health Research Institute, Department of Obstetrics an, University of Alberta, Edmonton, Canada
Find articles by Moldenhauer, L. in: JCI | PubMed | Google Scholar |
1Robinson Research Institute and School of Biomedicine, The University of Adelaide, Adelaide, Australia
2Robinson Research Institute and School of Biomedicine, The University of Adelaide, Adelaide, United States of America
3Flinders Health and Medical Research Institute, Flinders University, Adelaide, Australia
4Women and Children’s Health Research Institute, Department of Obstetrics an, University of Alberta, Edmonton, Canada
Find articles by Tran, H. in: JCI | PubMed | Google Scholar
1Robinson Research Institute and School of Biomedicine, The University of Adelaide, Adelaide, Australia
2Robinson Research Institute and School of Biomedicine, The University of Adelaide, Adelaide, United States of America
3Flinders Health and Medical Research Institute, Flinders University, Adelaide, Australia
4Women and Children’s Health Research Institute, Department of Obstetrics an, University of Alberta, Edmonton, Canada
Find articles by Chan, H. in: JCI | PubMed | Google Scholar |
1Robinson Research Institute and School of Biomedicine, The University of Adelaide, Adelaide, Australia
2Robinson Research Institute and School of Biomedicine, The University of Adelaide, Adelaide, United States of America
3Flinders Health and Medical Research Institute, Flinders University, Adelaide, Australia
4Women and Children’s Health Research Institute, Department of Obstetrics an, University of Alberta, Edmonton, Canada
Find articles by Groome, H. in: JCI | PubMed | Google Scholar
1Robinson Research Institute and School of Biomedicine, The University of Adelaide, Adelaide, Australia
2Robinson Research Institute and School of Biomedicine, The University of Adelaide, Adelaide, United States of America
3Flinders Health and Medical Research Institute, Flinders University, Adelaide, Australia
4Women and Children’s Health Research Institute, Department of Obstetrics an, University of Alberta, Edmonton, Canada
Find articles by Lovell, E. in: JCI | PubMed | Google Scholar
1Robinson Research Institute and School of Biomedicine, The University of Adelaide, Adelaide, Australia
2Robinson Research Institute and School of Biomedicine, The University of Adelaide, Adelaide, United States of America
3Flinders Health and Medical Research Institute, Flinders University, Adelaide, Australia
4Women and Children’s Health Research Institute, Department of Obstetrics an, University of Alberta, Edmonton, Canada
Find articles by Green, E. in: JCI | PubMed | Google Scholar
1Robinson Research Institute and School of Biomedicine, The University of Adelaide, Adelaide, Australia
2Robinson Research Institute and School of Biomedicine, The University of Adelaide, Adelaide, United States of America
3Flinders Health and Medical Research Institute, Flinders University, Adelaide, Australia
4Women and Children’s Health Research Institute, Department of Obstetrics an, University of Alberta, Edmonton, Canada
Find articles by O'Hara, S. in: JCI | PubMed | Google Scholar |
1Robinson Research Institute and School of Biomedicine, The University of Adelaide, Adelaide, Australia
2Robinson Research Institute and School of Biomedicine, The University of Adelaide, Adelaide, United States of America
3Flinders Health and Medical Research Institute, Flinders University, Adelaide, Australia
4Women and Children’s Health Research Institute, Department of Obstetrics an, University of Alberta, Edmonton, Canada
Find articles by Roberts, C. in: JCI | PubMed | Google Scholar |
1Robinson Research Institute and School of Biomedicine, The University of Adelaide, Adelaide, Australia
2Robinson Research Institute and School of Biomedicine, The University of Adelaide, Adelaide, United States of America
3Flinders Health and Medical Research Institute, Flinders University, Adelaide, Australia
4Women and Children’s Health Research Institute, Department of Obstetrics an, University of Alberta, Edmonton, Canada
Find articles by Foyle, K. in: JCI | PubMed | Google Scholar
1Robinson Research Institute and School of Biomedicine, The University of Adelaide, Adelaide, Australia
2Robinson Research Institute and School of Biomedicine, The University of Adelaide, Adelaide, United States of America
3Flinders Health and Medical Research Institute, Flinders University, Adelaide, Australia
4Women and Children’s Health Research Institute, Department of Obstetrics an, University of Alberta, Edmonton, Canada
Find articles by Davidge, S. in: JCI | PubMed | Google Scholar |
1Robinson Research Institute and School of Biomedicine, The University of Adelaide, Adelaide, Australia
2Robinson Research Institute and School of Biomedicine, The University of Adelaide, Adelaide, United States of America
3Flinders Health and Medical Research Institute, Flinders University, Adelaide, Australia
4Women and Children’s Health Research Institute, Department of Obstetrics an, University of Alberta, Edmonton, Canada
Find articles by Robertson, S. in: JCI | PubMed | Google Scholar |
1Robinson Research Institute and School of Biomedicine, The University of Adelaide, Adelaide, Australia
2Robinson Research Institute and School of Biomedicine, The University of Adelaide, Adelaide, United States of America
3Flinders Health and Medical Research Institute, Flinders University, Adelaide, Australia
4Women and Children’s Health Research Institute, Department of Obstetrics an, University of Alberta, Edmonton, Canada
Find articles by Care, A. in: JCI | PubMed | Google Scholar |
Published December 10, 2024 - More info
Regulatory T (Treg) cells are essential for maternal immune tolerance of the fetus and placenta. In preeclampsia, aberrant Treg cell tolerance is implicated, but whether and how Treg cells affect the uterine vascular dysfunction thought to precede placental impairment and maternal vasculopathy is unclear. We utilized Foxp3DTR mice to test the hypothesis that Treg cells are essential regulators of decidual spiral artery adaptation to pregnancy. Transient Treg cell depletion during early placental morphogenesis caused impaired remodeling of decidual spiral arteries, altered uterine artery function and led to fewer DBA+ uterine natural killer (uNK) cells, resulting in late gestation fetal loss and fetal growth restriction. Replacing the Treg cells by transfer from wild-type donors mitigated the impact on uNK cells, vascular remodeling, and fetal loss. RNA sequencing of decidua revealed genes associated with NK cell function and placental extravillous trophoblasts were dysregulated after Treg cell depletion, and normalized by Treg cell replacement. These data implicate Treg cells as essential upstream drivers of uterine vascular adaptation to pregnancy, through a mechanism likely involving phenotypic regulation of uNK cells and trophoblast invasion. The findings provide insight into mechanisms linking impaired adaptive immune tolerance and altered spiral artery remodeling, two hallmark features of preeclampsia.