Proliferation of endogenous regulatory T cells improve the pathophysiology associated with placental ischaemia of pregnancy

Tarek Ibrahim, Lukasz Przybyl, Ashlyn C. Harmon, Lorena M. Amaral, Jessica L. Faulkner, Denise C. Cornelius, Mark W. Cunningham, Thomas Hünig, Florian Herse, Gerd Wallukat, Ralf Dechend, Babbette LaMarca

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Problem: Preeclampsia (PE) is associated with inflammation and decreased Treg cells and IL-10. The reduced uterine perfusion pressure (RUPP) rat model of PE exhibits these characteristics, and we hypothesized that induction of endogenous Tregs by a specific stimulus (CD28 superagonistic monoclonal antibody) would reduce inflammation, vasoactive factors, and hypertension in RUPP rats. Method of study: RUPP was performed at gestation day (GD) 14; CD28 superagonist was administered intraperitoneally GD15; GD18 carotid catheters were inserted, and GD19 MAP and pup weight, blood, and tissues were collected. Results: MAP (mmHg) in NP rats was 99±5 and 122±2 in RUPPs and was 111±1 mmHg in RUPP+SA. Circulating Tregs were 6±2% in NP rats and 0.77±0.49% in RUPP rats but increased to 11± 3% in RUPP+SA rats. Circulating IL-6 and IL-2 were decreased while IL-10 and TGF-B were significantly increased in RUPP+SA compared to RUPP controls. Vasoactive pathways such as ET-1, AT1-AA, and ROS were all reduced in RUPP+SA compared to RUPP. Pup weight was 2.4±0.05 mg in NP and 1.94±0.062 mg in RUPP and increased to 2.1± 0.05 mg in RUPP+SA. Conclusion: These data suggest that stimulating endogenous Tregs lower factors causing hypertension and can improve fetal weight in response to PE.

Original languageEnglish (US)
Article numbere12724
JournalAmerican Journal of Reproductive Immunology
Volume78
Issue number5
DOIs
StatePublished - 2017
Externally publishedYes

Keywords

  • inflammation
  • preeclampsia
  • regulatory T cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Reproductive Medicine
  • Obstetrics and Gynecology

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