The Role of Regulatory T Cells and Their Therapeutic Potential in Hypertensive Disease of Pregnancy: A Literature Review

Author:

Headen Kyle12,Jakaite Vaidile2ORCID,Mesaric Vita Andreja2ORCID,Scotta Cristiano3ORCID,Lombardi Giovanna3,Nicolaides Kypros H.12,Shangaris Panicos1234ORCID

Affiliation:

1. Department of Women and Children’s Health, School of Life Course Sciences, Faculty of Life Sciences & Medicine, King’s College London, London SE5 8AF, UK

2. Harris Birthright Research Centre for Fetal Medicine, King’s College Hospital, London SE5 8BB, UK

3. Peter Gorer Department of Immunobiology, School of Immunology & Microbial Sciences, Faculty of Life Sciences & Medicine, King’s College London, London SE1 1UL, UK

4. Immunoregulation Laboratory, Faculty of Life Sciences & Medicine, 5th Floor, Bermondsey Wing, Guy’s Hospital, London SE1 9RT, UK

Abstract

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.

Funder

Fetal Medicine Foundation Senior Clinical Lectureship and grants from the Fetal Medicine Foundation

Fetal Medicine Foundation PhD studentship

Fetal Medicine Foundation

Publisher

MDPI AG

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