{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:32:42Z","timestamp":1792805562984,"version":"4.5.0"},"reference-count":78,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,4,30]],"date-time":"2024-04-30T00:00:00Z","timestamp":1714435200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fetal Medicine Foundation Senior Clinical Lectureship and grants from the Fetal Medicine Foundation","award":["1037116"],"award-info":[{"award-number":["1037116"]}],"id":[{"id":"https:\/\/ror.org\/0261b7b91","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Fetal Medicine Foundation PhD studentship","award":["1037116"],"award-info":[{"award-number":["1037116"]}],"id":[{"id":"https:\/\/ror.org\/0261b7b91","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Fetal Medicine Foundation","award":["1037116"],"award-info":[{"award-number":["1037116"]}],"id":[{"id":"https:\/\/ror.org\/0261b7b91","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hypertensive disorders of pregnancy (HDP), including preeclampsia (PE) and gestational hypertension (GH), are major causes of maternal and foetal morbidity and mortality. This review elucidates the role of regulatory T cells (Tregs) in the immunological aspects of HDP and explores their therapeutic potential. Tregs, which play a critical role in maintaining immune homeostasis, are crucial in pregnancy to prevent immune-mediated rejection of the foetus. The review highlights that Tregs contribute to immunological adaptation in normal pregnancy, ensuring foetal acceptance. In contrast, HDP is associated with Treg dysfunction, which is marked by decreased numbers and impaired regulatory capacity, leading to inadequate immune tolerance and abnormal placental development. This dysfunction is particularly evident in PE, in which Tregs fail to adequately modulate the maternal immune response against foetal antigens, contributing to the pathophysiology of the disorder. Therapeutic interventions aiming to modulate Treg activity represent a promising avenue for HDP management. Studies in animal models and limited clinical trials suggest that enhancing Treg functionality could mitigate HDP symptoms and improve pregnancy outcomes. However, given the multifactorial nature of HDP and the intricate regulatory mechanisms of Tregs, the review explores the complexities of translating in vitro and animal model findings into effective clinical therapies. In conclusion, while the precise role of Tregs in HDP is still being unravelled, their central role in immune regulation during pregnancy is indisputable. Further research is needed to fully understand the mechanisms by which Tregs contribute to HDP and to develop targeted therapies that can safely and effectively harness their regulatory potential for treating hypertensive diseases of pregnancy.<\/jats:p>","DOI":"10.3390\/ijms25094884","type":"journal-article","created":{"date-parts":[[2024,5,1]],"date-time":"2024-05-01T03:30:49Z","timestamp":1714534249000},"page":"4884","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["The Role of Regulatory T Cells and Their Therapeutic Potential in Hypertensive Disease of Pregnancy: A Literature Review"],"prefix":"10.3390","volume":"25","author":[{"given":"Kyle","family":"Headen","sequence":"first","affiliation":[{"name":"Department of Women and Children\u2019s Health, School of Life Course Sciences, Faculty of Life Sciences & Medicine, King\u2019s College London, London SE5 8AF, UK"},{"name":"Harris Birthright Research Centre for Fetal Medicine, King\u2019s College Hospital, London SE5 8BB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4688-5751","authenticated-orcid":false,"given":"Vaidile","family":"Jakaite","sequence":"additional","affiliation":[{"name":"Harris Birthright Research Centre for Fetal Medicine, King\u2019s College Hospital, London SE5 8BB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1214-344X","authenticated-orcid":false,"given":"Vita Andreja","family":"Mesaric","sequence":"additional","affiliation":[{"name":"Harris Birthright Research Centre for Fetal Medicine, King\u2019s College Hospital, London SE5 8BB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3942-5201","authenticated-orcid":false,"given":"Cristiano","family":"Scotta","sequence":"additional","affiliation":[{"name":"Peter Gorer Department of Immunobiology, School of Immunology & Microbial Sciences, Faculty of Life Sciences & Medicine, King\u2019s College London, London SE1 1UL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna","family":"Lombardi","sequence":"additional","affiliation":[{"name":"Peter Gorer Department of Immunobiology, School of Immunology & Microbial Sciences, Faculty of Life Sciences & Medicine, King\u2019s College London, London SE1 1UL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kypros H.","family":"Nicolaides","sequence":"additional","affiliation":[{"name":"Department of Women and Children\u2019s Health, School of Life Course Sciences, Faculty of Life Sciences & Medicine, King\u2019s College London, London SE5 8AF, UK"},{"name":"Harris Birthright Research Centre for Fetal Medicine, King\u2019s College Hospital, London SE5 8BB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2750-8405","authenticated-orcid":false,"given":"Panicos","family":"Shangaris","sequence":"additional","affiliation":[{"name":"Department of Women and Children\u2019s Health, School of Life Course Sciences, Faculty of Life Sciences & Medicine, King\u2019s College London, London SE5 8AF, UK"},{"name":"Harris Birthright Research Centre for Fetal Medicine, King\u2019s College Hospital, London SE5 8BB, UK"},{"name":"Peter Gorer Department of Immunobiology, School of Immunology & Microbial Sciences, Faculty of Life Sciences & Medicine, King\u2019s College London, London SE1 1UL, UK"},{"name":"Immunoregulation Laboratory, Faculty of Life Sciences & Medicine, 5th Floor, Bermondsey Wing, Guy\u2019s Hospital, London SE1 9RT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1298","DOI":"10.1038\/s41440-022-00965-6","article-title":"Hypertensive disorders of pregnancy: Definition, management, and out-of-office blood pressure measurement","volume":"45","author":"Metoki","year":"2022","journal-title":"Hypertens. Res."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Jiang, L., Tang, C., Gong, Y., Liu, Y., Rao, J., Chen, S., Qu, W., Wu, D., Lei, L., and Chen, L. (2018). PD-1\/PD-L1 regulates Treg differentiation in pregnancy-induced hypertension. Braz. J. Med. Biol. Res., 51.","DOI":"10.1590\/1414-431x20187334"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"544.e1","DOI":"10.1016\/j.ajog.2013.08.019","article-title":"Incidence of preeclampsia: Risk factors and outcomes associated with early- versus late-onset disease","volume":"209","author":"Lisonkova","year":"2013","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1097\/MNH.0000000000000870","article-title":"Novel therapeutic and diagnostic approaches for preeclampsia","volume":"32","author":"Vatish","year":"2023","journal-title":"Curr. Opin. Nephrol. Hypertens."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1817","DOI":"10.1056\/NEJMra2109523","article-title":"Preeclampsia","volume":"386","author":"Magee","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.ajog.2019.11.1247","article-title":"The competing risk approach for prediction of preeclampsia","volume":"223","author":"Wright","year":"2020","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e072157","DOI":"10.1136\/bmj-2022-072157","article-title":"Maternal hypertensive disorder of pregnancy and mortality in offspring from birth to young adulthood: National population based cohort study","volume":"379","author":"Huang","year":"2022","journal-title":"BMJ"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Zakiyah, N., Tuytten, R., Baker, P.N., Kenny, L.C., Postma, M.J., van Asselt, A.D.I., and on behalf of IMPROvED Consortium (2022). Early cost-effectiveness analysis of screening for preeclampsia in nulliparous women: A modelling approach in European high-income settings. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0267313"},{"key":"ref_9","unstructured":"National Institute for Health and Care Excellence (NICE) (2023). NICE Guideline 133, NICE."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"737862","DOI":"10.3389\/fimmu.2021.737862","article-title":"Regulatory T Cells in Pregnancy Adverse Outcomes: A Systematic Review and Meta-Analysis","volume":"12","author":"Green","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"McElwain, C.J., McCarthy, F.P., and McCarthy, C.M. (2021). Gestational Diabetes Mellitus and Maternal Immune Dysregulation: What We Know So Far. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22084261"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1007\/s12026-014-8512-5","article-title":"Regulatory T cells and their roles in immune dysregulation and allergy","volume":"58","author":"Pellerin","year":"2014","journal-title":"Immunol. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1126\/science.1079490","article-title":"Control of Regulatory T Cell Development by the Transcription Factor Foxp3","volume":"299","author":"Hori","year":"2003","journal-title":"Science"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1159\/000527336","article-title":"Reconsideration of the Role of Regulatory T Cells during Pregnancy: Differential Characteristics of Regulatory T Cells between the Maternal-Fetal Interface and Peripheral Sites and between Early and Late Pregnancy","volume":"31","author":"Saito","year":"2022","journal-title":"Med. Princ. Pr."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4224","DOI":"10.1172\/JCI122182","article-title":"Regulatory T cells in embryo implantation and the immune response to pregnancy","volume":"128","author":"Robertson","year":"2018","journal-title":"J. Clin. Investig."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1111\/imr.12160","article-title":"tTregs, pTregs, and iTregs: Similarities and differences","volume":"259","author":"Shevach","year":"2014","journal-title":"Immunol. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"925135","DOI":"10.1155\/2012\/925135","article-title":"CD4 + T Cells: Differentiation and Functions","volume":"2012","author":"Luckheeram","year":"2012","journal-title":"Clin. Dev. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1002\/eji.201948131","article-title":"Treg cell therapy: How cell heterogeneity can make the difference","volume":"51","author":"Giganti","year":"2021","journal-title":"Eur. J. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"253","DOI":"10.3389\/fimmu.2013.00253","article-title":"Peripheral and thymic foxp3(+) regulatory T cells in search of origin, distinction, and function","volume":"4","author":"Dhamne","year":"2013","journal-title":"Front. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4871","DOI":"10.1182\/blood-2004-10-3888","article-title":"CD25+CD4+ regulatory T cells generated by exposure to a model protein antigen prevent allograft rejection: Antigen-specific reactivation in vivo is critical for bystander regulation","volume":"105","author":"Karim","year":"2005","journal-title":"Blood"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1723","DOI":"10.1084\/jem.20120914","article-title":"Neuropilin 1 is expressed on thymus-derived natural regulatory T cells, but not mucosa-generated induced Foxp3+ T reg cells","volume":"209","author":"Weiss","year":"2012","journal-title":"J. Exp. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"51","DOI":"10.3389\/fimmu.2012.00051","article-title":"Molecular Mechanisms of Treg-Mediated T Cell Suppression","volume":"3","author":"Schmidt","year":"2012","journal-title":"Front. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1111\/j.1365-2567.2006.02362.x","article-title":"Cytotoxic T lymphocyte antigen-4-dependent down-modulation of costimulatory molecules on dendritic cells in CD4+ CD25+ regulatory T-cell-mediated suppression","volume":"118","author":"Oderup","year":"2006","journal-title":"Immunology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"10113","DOI":"10.1073\/pnas.0711106105","article-title":"Foxp3+ natural regulatory T cells preferentially form aggregates on dendritic cells in vitro and actively inhibit their maturation","volume":"105","author":"Onishi","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1038\/s41590-022-01289-w","article-title":"Differences in CD80 and CD86 transendocytosis reveal CD86 as a key target for CTLA-4 immune regulation","volume":"23","author":"Kennedy","year":"2022","journal-title":"Nat. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"5916","DOI":"10.4049\/jimmunol.180.9.5916","article-title":"Regulatory T Cells Inhibit Dendritic Cells by Lymphocyte Activation Gene-3 Engagement of MHC Class II","volume":"180","author":"Liang","year":"2008","journal-title":"J. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1016\/j.immuni.2004.08.010","article-title":"Role of LAG-3 in Regulatory T Cells","volume":"21","author":"Huang","year":"2004","journal-title":"Immunity"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1126\/science.1160062","article-title":"CTLA-4 Control over Foxp3+ Regulatory T Cell Function","volume":"322","author":"Wing","year":"2008","journal-title":"Science"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1111\/j.1365-2567.2008.02813.x","article-title":"Mechanisms of regulatory T-cell suppression\u2014A diverse arsenal for a moving target","volume":"124","author":"Sojka","year":"2008","journal-title":"Immunology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1084\/jem.20102149","article-title":"Memory\/effector (CD45RBlo) CD4 T cells are controlled directly by IL-10 and cause IL-22\u2013dependent intestinal pathology","volume":"208","author":"Kamanaka","year":"2011","journal-title":"J. Exp. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"18336","DOI":"10.1073\/pnas.1110566108","article-title":"Regulatory T cells inhibit acute IFN-\u03b3 synthesis without blocking T-helper cell type 1 (Th1) differentiation via a compartmentalized requirement for IL-10","volume":"108","author":"Sojka","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1038\/nature06306","article-title":"The inhibitory cytokine IL-35 contributes to regulatory T-cell function","volume":"450","author":"Collison","year":"2007","journal-title":"Nature"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"616949","DOI":"10.3389\/fimmu.2020.616949","article-title":"The Complex Role of Regulatory T Cells in Immunity and Aging","volume":"11","author":"Melzer","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1111\/imm.13208","article-title":"Tissue regulatory T cells","volume":"161","author":"Lui","year":"2020","journal-title":"Immunology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1016\/j.cell.2008.05.009","article-title":"Regulatory T cells and immune tolerance","volume":"133","author":"Sakaguchi","year":"2008","journal-title":"Cell"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2964","DOI":"10.1093\/humrep\/der301","article-title":"An imbalance in interleukin-17-producing T and Foxp3+ regulatory T cells in women with idiopathic recurrent pregnancy loss","volume":"26","author":"Lee","year":"2011","journal-title":"Hum. Reprod."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.3389\/fimmu.2020.01182","article-title":"Regulatory T Cells in Pregnancy: It Is Not All About FoxP3","volume":"11","author":"Krop","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1016\/S0002-9440(10)62302-4","article-title":"Abnormal T-Cell Reactivity against Paternal Antigens in Spontaneous Abortion","volume":"166","author":"Zenclussen","year":"2005","journal-title":"Am. J. Pathol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2537","DOI":"10.1016\/j.celrep.2019.04.109","article-title":"Three Types of Functional Regulatory T Cells Control T Cell Responses at the Human Maternal-Fetal Interface","volume":"27","author":"Benner","year":"2019","journal-title":"Cell Rep."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.jri.2010.02.006","article-title":"Regulatory T cells are necessary for implantation and maintenance of early pregnancy but not late pregnancy in allogeneic mice","volume":"85","author":"Shima","year":"2010","journal-title":"J. Reprod. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1111\/j.1600-0897.2011.01040.x","article-title":"Uterine Regulatory T cells, IL-10 and Hypertension","volume":"66","author":"Nevers","year":"2011","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.chom.2011.06.005","article-title":"Foxp3+ Regulatory T Cell Expansion Required for Sustaining Pregnancy Compromises Host Defense against Prenatal Bacterial Pathogens","volume":"10","author":"Rowe","year":"2011","journal-title":"Cell Host Microb."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"478","DOI":"10.3389\/fimmu.2019.00478","article-title":"Therapeutic Potential of Regulatory T Cells in Preeclampsia\u2014Opportunities and Challenges","volume":"10","author":"Robertson","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3521","DOI":"10.4049\/jimmunol.1003947","article-title":"Foxp3+-Inducible Regulatory T Cells Suppress Endothelial Activation and Leukocyte Recruitment","volume":"187","author":"Bu","year":"2011","journal-title":"J. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1016\/j.ajpath.2010.11.034","article-title":"Natural Regulatory T Cells Control Coronary Arteriolar Endothelial Dysfunction in Hypertensive Mice","volume":"178","author":"Matrougui","year":"2011","journal-title":"Am. J. Pathol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.ajog.2010.08.009","article-title":"The \u201cGreat Obstetrical Syndromes\u201d are associated with disorders of deep placentation","volume":"204","author":"Brosens","year":"2011","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1111\/aji.12234","article-title":"Immunological Modes of Pregnancy Loss: Inflammation, Immune Effectors, and Stress","volume":"72","author":"Bao","year":"2014","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1089\/dna.2017.4005","article-title":"Functional Defects of Regulatory T Cell Through Interleukin 10 Mediated Mechanism in the Induction of Gestational Diabetes Mellitus","volume":"37","author":"Yang","year":"2018","journal-title":"DNA Cell Biol."},{"key":"ref_49","first-page":"190","article-title":"Expression and production of interleu-kin-10 by human trophoblast: Relationship to pregnancy immunotolerance","volume":"3","author":"Bennett","year":"1997","journal-title":"Early Pregnancy"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.bpobgyn.2011.02.006","article-title":"Placental bed disorders in preterm labor, preterm PROM, spontaneous abortion and abruptio placentae","volume":"25","author":"Romero","year":"2011","journal-title":"Best Pr. Res. Clin. Obstet. Gynaecol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1314","DOI":"10.1038\/ajh.2009.185","article-title":"Toll-like receptor 3 activation during pregnancy elicits preeclampsia-like symptoms in rats","volume":"22","author":"Tinsley","year":"2009","journal-title":"Am. J. Hypertens."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.4049\/jimmunol.0900788","article-title":"TLR9 activation coupled to IL-10 deficiency induces adverse pregnancy outcomes","volume":"183","author":"Thaxton","year":"2009","journal-title":"J. Immunol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1161\/HYPERTENSIONAHA.110.163329","article-title":"A critical role of interleukin-10 in modulating hypoxia-induced preeclampsia-like disease in mice","volume":"57","author":"Lai","year":"2011","journal-title":"Hypertension"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1210\/jc.2003-031244","article-title":"First trimester placental growth factor and soluble fms-like tyrosine kinase 1 and risk for preeclampsia","volume":"89","author":"Thadhani","year":"2004","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1038\/nm1429","article-title":"Soluble endoglin contributes to the pathogenesis of preeclampsia","volume":"12","author":"Venkatesha","year":"2006","journal-title":"Nat. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1111\/j.1365-2249.2007.03397.x","article-title":"Proportion of peripheral blood and decidual CD4+ CD25bright regulatory T cells in pre-eclampsia","volume":"149","author":"Sasaki","year":"2007","journal-title":"Clin. Exp. Immunol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3088","DOI":"10.1172\/JCI97490","article-title":"Nox2 in regulatory T cells promotes angiotensin II\u2013induced cardiovascular remodeling","volume":"128","author":"Emmerson","year":"2018","journal-title":"J. Clin. Investig."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1586\/1744666X.2016.1105740","article-title":"Regulatory T-cells and preeclampsia: An overview of literature","volume":"12","author":"Rahimzadeh","year":"2016","journal-title":"Expert Rev. Clin. Immunol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"7023","DOI":"10.4049\/jimmunol.0901154","article-title":"Systemic Increase in the Ratio between Foxp3+ and IL-17-Producing CD4+ T Cells in Healthy Pregnancy but Not in Preeclampsia","volume":"183","author":"Peek","year":"2009","journal-title":"J. Immunol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.jri.2011.05.006","article-title":"The unique pathophysiology of early-onset severe preeclampsia: Role of decidual T regulatory cells","volume":"91","author":"Quinn","year":"2011","journal-title":"J. Reprod. Immunol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1038\/s41581-022-00670-0","article-title":"The role of immune cells and mediators in preeclampsia","volume":"19","author":"Deer","year":"2023","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/j.clim.2008.07.032","article-title":"Distinct subsets of regulatory T cells during pregnancy: Is the imbalance of these subsets involved in the pathogenesis of preeclampsia?","volume":"129","author":"Steinborn","year":"2008","journal-title":"Clin. Immunol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.3389\/fimmu.2019.01305","article-title":"Differential Dynamics of the Maternal Immune System in Healthy Pregnancy and Preeclampsia","volume":"10","author":"Han","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"291","DOI":"10.3109\/10641955.2015.1032054","article-title":"IL-10 supplementation increases Tregs and decreases hypertension in the RUPP rat model of preeclampsia","volume":"34","author":"Harmon","year":"2015","journal-title":"Hypertens. Pregnancy"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1093\/humrep\/deu014","article-title":"Adoptive transfer of pregnancy-induced CD4+CD25+ regulatory T cells reverses the increase in abortion rate caused by interleukin 17 in the CBA\/J\u00d7BALB\/c mouse model","volume":"29","author":"Wang","year":"2014","journal-title":"Hum. Reprod."},{"key":"ref_66","first-page":"220","article-title":"Adoptive cell therapy with induced regulatory T cells normalises the abortion rate in abortion-prone mice","volume":"33","author":"Idali","year":"2020","journal-title":"Reprod. Fertil. Dev."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.ejogrb.2011.12.023","article-title":"Adoptive transfer of CD4+CD25+ regulatory T cells for prevention and treatment of spon-taneous abortion","volume":"161","author":"Yin","year":"2012","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"13938","DOI":"10.1038\/srep13938","article-title":"Transfer of regulatory T cells into abor-tion-prone mice promotes the expansion of uterine mast cells and normalizes early pregnancy angiogenesis","volume":"5","author":"Woidacki","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2683","DOI":"10.1002\/eji.201142317","article-title":"Progesterone suppresses the mTOR pathway and promotes generation of induced regulatory T cells with increased stability","volume":"42","author":"Lee","year":"2012","journal-title":"Eur. J. Immunol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"e021619","DOI":"10.1136\/bmjopen-2018-021619","article-title":"Development of a core outcome set for im-munomodulation in pregnancy (COSIMPREG): A protocol for a systematic review and Delphi study","volume":"8","author":"Prins","year":"2018","journal-title":"BMJ Open"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.autrev.2014.10.011","article-title":"GITR+ regulatory T cells in the treatment of autoimmune diseases","volume":"14","author":"Petrillo","year":"2015","journal-title":"Autoimmun. Rev."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1038\/icb.2012.18","article-title":"Inhibition of activation induced CD154 on CD4+ CD25\u2212 cells: A valid surrogate for human Treg suppressor function","volume":"90","author":"Hill","year":"2012","journal-title":"Immunol. Cell Biol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1016\/S0140-6736(20)30167-7","article-title":"Regulatory cell therapy in kidney transplantation (The ONE Study): A harmonised design and analysis of seven non-randomised, single-arm, phase 1\/2A trials","volume":"395","author":"Sawitzki","year":"2020","journal-title":"Lancet"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.jri.2013.07.006","article-title":"Cumulative exposure to paternal seminal fluid prior to conception and subsequent risk of preeclampsia","volume":"101\u2013102","author":"Saftlas","year":"2014","journal-title":"J. Reprod. Immunol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.1038\/s41598-018-19263-8","article-title":"Periconception onset diabetes is associated with embryopathy and fetal growth retardation, reproductive tract hyperglycosylation and impaired immune adaptation to pregnancy","volume":"8","author":"Brown","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1778","DOI":"10.4049\/jimmunol.1003919","article-title":"Progesterone promotes differentiation of human cord blood fetal T cells into T regulatory cells but suppresses their differentiation into Th17 cells","volume":"187","author":"Lee","year":"2011","journal-title":"J. Immunol."},{"key":"ref_77","first-page":"1125","article-title":"Applicability, safety, and biological activity of regulatory T cell therapy in liver transplantation","volume":"20","author":"Whitehouse","year":"2019","journal-title":"Am. J. Transplant."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"e061864","DOI":"10.1136\/bmjopen-2022-061864","article-title":"Transplantation Without Overimmunosuppression (TWO) study protocol: A phase 2b randomised controlled single-centre trial of regulatory T cell therapy to facilitate immuno-suppression reduction in living donor kidney transplant recipients","volume":"12","author":"Brook","year":"2022","journal-title":"BMJ Open"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/9\/4884\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:36:55Z","timestamp":1760107015000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/9\/4884"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,30]]},"references-count":78,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2024,5]]}},"alternative-id":["ijms25094884"],"URL":"https:\/\/doi.org\/10.3390\/ijms25094884","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,30]]}}}