Cellular Immunotherapy in Mice Prevents Maternal Hypertension and Restores Anti-Inflammatory Cytokine Balance in Maternal and Fetal Tissues
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 cardiovasc...
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MDPI AG
2023-09-01
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| Series: | International Journal of Molecular Sciences |
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| author | Gabrielle Gray Douglas G. Scroggins Katlin T. Wilson Sabrina M. Scroggins |
| author_facet | Gabrielle Gray Douglas G. Scroggins Katlin T. Wilson Sabrina M. Scroggins |
| author_sort | Gabrielle Gray |
| collection | DOAJ |
| description | 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<sub>H</sub>) 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. <i>C57BL/6J</i> 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<sub>H</sub>-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<sub>H</sub>-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. |
| first_indexed | 2024-03-10T23:20:44Z |
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| last_indexed | 2024-03-10T23:20:44Z |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-a31ee970be5d415089a5034f3901fea92023-11-19T08:19:32ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-09-0124171359410.3390/ijms241713594Cellular Immunotherapy in Mice Prevents Maternal Hypertension and Restores Anti-Inflammatory Cytokine Balance in Maternal and Fetal TissuesGabrielle Gray0Douglas G. Scroggins1Katlin T. Wilson2Sabrina M. Scroggins3Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USASchool of Medicine, Department of Biomedical Sciences, University of Minnesota Duluth, Duluth, MN 55812, USASchool of Medicine, Department of Biomedical Sciences, University of Minnesota Duluth, Duluth, MN 55812, USASchool of Medicine, Department of Biomedical Sciences, University of Minnesota Duluth, Duluth, MN 55812, USAPreeclampsia 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<sub>H</sub>) 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. <i>C57BL/6J</i> 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<sub>H</sub>-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<sub>H</sub>-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.https://www.mdpi.com/1422-0067/24/17/13594cellular therapypreeclampsiacytokinesinflammationregulatory dendritic cells |
| spellingShingle | Gabrielle Gray Douglas G. Scroggins Katlin T. Wilson Sabrina M. Scroggins Cellular Immunotherapy in Mice Prevents Maternal Hypertension and Restores Anti-Inflammatory Cytokine Balance in Maternal and Fetal Tissues International Journal of Molecular Sciences cellular therapy preeclampsia cytokines inflammation regulatory dendritic cells |
| title | Cellular Immunotherapy in Mice Prevents Maternal Hypertension and Restores Anti-Inflammatory Cytokine Balance in Maternal and Fetal Tissues |
| title_full | Cellular Immunotherapy in Mice Prevents Maternal Hypertension and Restores Anti-Inflammatory Cytokine Balance in Maternal and Fetal Tissues |
| title_fullStr | Cellular Immunotherapy in Mice Prevents Maternal Hypertension and Restores Anti-Inflammatory Cytokine Balance in Maternal and Fetal Tissues |
| title_full_unstemmed | Cellular Immunotherapy in Mice Prevents Maternal Hypertension and Restores Anti-Inflammatory Cytokine Balance in Maternal and Fetal Tissues |
| title_short | Cellular Immunotherapy in Mice Prevents Maternal Hypertension and Restores Anti-Inflammatory Cytokine Balance in Maternal and Fetal Tissues |
| title_sort | cellular immunotherapy in mice prevents maternal hypertension and restores anti inflammatory cytokine balance in maternal and fetal tissues |
| topic | cellular therapy preeclampsia cytokines inflammation regulatory dendritic cells |
| url | https://www.mdpi.com/1422-0067/24/17/13594 |
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