Cellular Immunotherapy in Mice Prevents Maternal Hypertension and Restores Anti-Inflammatory Cytokine Balance in Maternal and Fetal Tissues

Gabrielle Gray, Douglas G. Scroggins, Katlin T. Wilson, Sabrina M. Scroggins

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Preeclampsia is the leading cause of maternal–fetal morbidity worldwide. The concept that persistent feto-placental intolerance is important in the pathogenesis of preeclampsia (PreE) has been demonstrated by our lab and others. Arginine vasopressin (AVP) infusion during pregnancy induces cardiovascular, renal, and T helper (TH) cell alterations in mice consistent with human PreE. In addition to their conventional immuno-stimulatory role, dendritic cells (DCs) also play a vital role in immune tolerance. In contrast to conventional DCs, regulatory DCs (DCregs) express low levels of co-stimulatory markers, produce anti-inflammatory cytokines, induce T regulatory (Treg) cells, and promote tolerance. In mice, DCregs prevent pro-inflammatory responses and induce antigen-specific tolerance. Given these known functions of DCregs, we hypothesize that DCregs will prevent the development of AVP-induced PreE in mice. C57BL/6J females were infused with AVP (24 ng/h) or saline throughout gestation via an osmotic minipump. Bone-marrow-derived DCregs were injected into AVP-infused dams at the time of the pump implantation or on gestational day (GD) 7. The blood pressure of the mice was taken throughout their pregnancy. The maternal urine proteins and TH-associated cytokines in maternal and fetal tissues were measured on GD 18. The treatment with DCregs effectively prevented the elevation of maternal blood pressure, proteinuria, and fetal growth restriction that were observed in AVP-infused dams. Furthermore, we noted a reduction in the pro-inflammatory TH-associated cytokines IFNγ and IL-17, while anti-inflammatory cytokines IL-4, IL-10, and TGFβ showed an increase following DCreg treatment. These outcomes provide strong evidence supporting the potential of DCregs as a valuable therapeutic approach in addressing PreE.

Original languageEnglish (US)
Article number13594
JournalInternational journal of molecular sciences
Volume24
Issue number17
DOIs
StatePublished - Sep 2023

Bibliographical note

Publisher Copyright:
© 2023 by the authors.

Keywords

  • cellular therapy
  • cytokines
  • inflammation
  • preeclampsia
  • regulatory dendritic cells

PubMed: MeSH publication types

  • Journal Article

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