PMID- 37686399 OWN - NLM STAT- MEDLINE DCOM- 20230911 LR - 20230912 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 24 IP - 17 DP - 2023 Sep 2 TI - Cellular Immunotherapy in Mice Prevents Maternal Hypertension and Restores Anti-Inflammatory Cytokine Balance in Maternal and Fetal Tissues. LID - 10.3390/ijms241713594 [doi] LID - 13594 AB - 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 (T(H)) 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 T(H)-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 T(H)-associated cytokines IFNgamma and IL-17, while anti-inflammatory cytokines IL-4, IL-10, and TGFbeta showed an increase following DCreg treatment. These outcomes provide strong evidence supporting the potential of DCregs as a valuable therapeutic approach in addressing PreE. FAU - Gray, Gabrielle AU - Gray G AD - Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA. FAU - Scroggins, Douglas G AU - Scroggins DG AD - School of Medicine, Department of Biomedical Sciences, University of Minnesota Duluth, Duluth, MN 55812, USA. FAU - Wilson, Katlin T AU - Wilson KT AD - School of Medicine, Department of Biomedical Sciences, University of Minnesota Duluth, Duluth, MN 55812, USA. FAU - Scroggins, Sabrina M AU - Scroggins SM AUID- ORCID: 0000-0001-5842-0575 AD - School of Medicine, Department of Biomedical Sciences, University of Minnesota Duluth, Duluth, MN 55812, USA. LA - eng GR - K01 HL155240/HL/NHLBI NIH HHS/United States GR - UL1 TR002494/TR/NCATS NIH HHS/United States GR - UL1TR002494/TR/NCATS NIH HHS/United States GR - KL2 TR002492/TR/NCATS NIH HHS/United States GR - KL2TR002492/TR/NCATS NIH HHS/United States PT - Journal Article DEP - 20230902 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Cytokines) RN - 113-79-1 (Arginine Vasopressin) RN - 0 (Anti-Inflammatory Agents) SB - IM MH - Pregnancy MH - Humans MH - Female MH - Animals MH - Mice MH - Mice, Inbred C57BL MH - Cytokines MH - *Pre-Eclampsia/therapy MH - Placenta MH - Immunotherapy MH - Fetus MH - Arginine Vasopressin MH - Anti-Inflammatory Agents MH - *Hypertension PMC - PMC10487605 OTO - NOTNLM OT - cellular therapy OT - cytokines OT - inflammation OT - preeclampsia OT - regulatory dendritic cells COIS- The authors declare no conflict of interest. EDAT- 2023/09/09 11:45 MHDA- 2023/09/11 06:42 PMCR- 2023/09/02 CRDT- 2023/09/09 01:13 PHST- 2023/08/15 00:00 [received] PHST- 2023/08/29 00:00 [revised] PHST- 2023/09/01 00:00 [accepted] PHST- 2023/09/11 06:42 [medline] PHST- 2023/09/09 11:45 [pubmed] PHST- 2023/09/09 01:13 [entrez] PHST- 2023/09/02 00:00 [pmc-release] AID - ijms241713594 [pii] AID - ijms-24-13594 [pii] AID - 10.3390/ijms241713594 [doi] PST - epublish SO - Int J Mol Sci. 2023 Sep 2;24(17):13594. doi: 10.3390/ijms241713594.