The Immunomodulatory Role of Regulatory T Cells in Preterm Birth and Associated Pregnancy Outcomes

Nicoleta Mureanu; Amanda M Bowman; Imogen A Porter-Wright; Priya Verma; Athina Efthymiou; Kypros H Nicolaides; Cristiano Scotta; Giovanna Lombardi; Rachel M Tribe; Panicos Shangaris

doi:10.3390/ijms252211878

The Immunomodulatory Role of Regulatory T Cells in Preterm Birth and Associated Pregnancy Outcomes

Nicoleta Mureanu, Amanda M Bowman, Imogen A Porter-Wright, Priya Verma, Athina Efthymiou, Kypros H Nicolaides, Cristiano Scotta, Giovanna Lombardi, Rachel M Tribe, Panicos Shangaris

Research output: Contribution to journal › Review article › peer-review

Abstract

Spontaneous preterm birth (sPTB), defined as live birth before 37 weeks of gestational age, is associated with immune dysregulation and pro-inflammatory conditions that profoundly impact newborn health. The question of immune integrity at the maternal-foetal interface is a focus of recent studies centring not only sPTB but the conditions often affiliated with this outcome. Regulatory T cells (Tregs) play a critical anti-inflammatory role in pregnancy, promoting foetal tolerance and placentation. Due to this gestational role, it is hypothesised that decreased or dysfunctional Tregs may be implicated in cases of sPTB. This review examines studies comparing Treg presence in healthy term pregnancies and those with sPTB-associated conditions. Conflicting findings across different conditions and within sPTB itself have been identified. However, notable findings from the research indicate increased proinflammatory cytokines in pregnancies suffering from premature rupture of membranes (pPROM), chorioamnionitis, infection, preeclampsia, and gestational diabetes (GDM). Additionally, reduced Treg levels were identified in preeclampsia, GDM, and pPROM as well as chorioamnionitis presenting with increased Treg dysfunctionality. Treg deficiencies may contribute to health issues in preterm newborns. Current sPTB treatments are limited, underscoring the potential of in utero therapies targeting inflammation, including T cell interventions. Future research aims to establish consensus on the role of Tregs in sPTB and associated conditions and advancing understanding of mechanisms leading to Treg deficiencies in adverse pregnancy outcomes.

Original language	English
Article number	11878
Journal	International Journal of Molecular Sciences
Volume	25
Issue number	22
DOIs	https://doi.org/10.3390/ijms252211878
Publication status	Published - 5 Nov 2024

Keywords

Humans
Pregnancy
T-Lymphocytes, Regulatory/immunology
Female
Premature Birth/immunology
Pregnancy Outcome
Immunomodulation
Infant, Newborn
Fetal Membranes, Premature Rupture/immunology
Diabetes, Gestational/immunology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3390/ijms252211878

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title = "The Immunomodulatory Role of Regulatory T Cells in Preterm Birth and Associated Pregnancy Outcomes",

abstract = "Spontaneous preterm birth (sPTB), defined as live birth before 37 weeks of gestational age, is associated with immune dysregulation and pro-inflammatory conditions that profoundly impact newborn health. The question of immune integrity at the maternal-foetal interface is a focus of recent studies centring not only sPTB but the conditions often affiliated with this outcome. Regulatory T cells (Tregs) play a critical anti-inflammatory role in pregnancy, promoting foetal tolerance and placentation. Due to this gestational role, it is hypothesised that decreased or dysfunctional Tregs may be implicated in cases of sPTB. This review examines studies comparing Treg presence in healthy term pregnancies and those with sPTB-associated conditions. Conflicting findings across different conditions and within sPTB itself have been identified. However, notable findings from the research indicate increased proinflammatory cytokines in pregnancies suffering from premature rupture of membranes (pPROM), chorioamnionitis, infection, preeclampsia, and gestational diabetes (GDM). Additionally, reduced Treg levels were identified in preeclampsia, GDM, and pPROM as well as chorioamnionitis presenting with increased Treg dysfunctionality. Treg deficiencies may contribute to health issues in preterm newborns. Current sPTB treatments are limited, underscoring the potential of in utero therapies targeting inflammation, including T cell interventions. Future research aims to establish consensus on the role of Tregs in sPTB and associated conditions and advancing understanding of mechanisms leading to Treg deficiencies in adverse pregnancy outcomes.",

keywords = "Humans, Pregnancy, T-Lymphocytes, Regulatory/immunology, Female, Premature Birth/immunology, Pregnancy Outcome, Immunomodulation, Infant, Newborn, Fetal Membranes, Premature Rupture/immunology, Diabetes, Gestational/immunology",

author = "Nicoleta Mureanu and Bowman, {Amanda M} and Porter-Wright, {Imogen A} and Priya Verma and Athina Efthymiou and Nicolaides, {Kypros H} and Cristiano Scotta and Giovanna Lombardi and Tribe, {Rachel M} and Panicos Shangaris",

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year = "2024",

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doi = "10.3390/ijms252211878",

language = "English",

volume = "25",

journal = "International Journal of Molecular Sciences",

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TY - JOUR

T1 - The Immunomodulatory Role of Regulatory T Cells in Preterm Birth and Associated Pregnancy Outcomes

AU - Mureanu, Nicoleta

AU - Bowman, Amanda M

AU - Porter-Wright, Imogen A

AU - Verma, Priya

AU - Efthymiou, Athina

AU - Nicolaides, Kypros H

AU - Scotta, Cristiano

AU - Lombardi, Giovanna

AU - Tribe, Rachel M

AU - Shangaris, Panicos

PY - 2024/11/5

Y1 - 2024/11/5

N2 - Spontaneous preterm birth (sPTB), defined as live birth before 37 weeks of gestational age, is associated with immune dysregulation and pro-inflammatory conditions that profoundly impact newborn health. The question of immune integrity at the maternal-foetal interface is a focus of recent studies centring not only sPTB but the conditions often affiliated with this outcome. Regulatory T cells (Tregs) play a critical anti-inflammatory role in pregnancy, promoting foetal tolerance and placentation. Due to this gestational role, it is hypothesised that decreased or dysfunctional Tregs may be implicated in cases of sPTB. This review examines studies comparing Treg presence in healthy term pregnancies and those with sPTB-associated conditions. Conflicting findings across different conditions and within sPTB itself have been identified. However, notable findings from the research indicate increased proinflammatory cytokines in pregnancies suffering from premature rupture of membranes (pPROM), chorioamnionitis, infection, preeclampsia, and gestational diabetes (GDM). Additionally, reduced Treg levels were identified in preeclampsia, GDM, and pPROM as well as chorioamnionitis presenting with increased Treg dysfunctionality. Treg deficiencies may contribute to health issues in preterm newborns. Current sPTB treatments are limited, underscoring the potential of in utero therapies targeting inflammation, including T cell interventions. Future research aims to establish consensus on the role of Tregs in sPTB and associated conditions and advancing understanding of mechanisms leading to Treg deficiencies in adverse pregnancy outcomes.

AB - Spontaneous preterm birth (sPTB), defined as live birth before 37 weeks of gestational age, is associated with immune dysregulation and pro-inflammatory conditions that profoundly impact newborn health. The question of immune integrity at the maternal-foetal interface is a focus of recent studies centring not only sPTB but the conditions often affiliated with this outcome. Regulatory T cells (Tregs) play a critical anti-inflammatory role in pregnancy, promoting foetal tolerance and placentation. Due to this gestational role, it is hypothesised that decreased or dysfunctional Tregs may be implicated in cases of sPTB. This review examines studies comparing Treg presence in healthy term pregnancies and those with sPTB-associated conditions. Conflicting findings across different conditions and within sPTB itself have been identified. However, notable findings from the research indicate increased proinflammatory cytokines in pregnancies suffering from premature rupture of membranes (pPROM), chorioamnionitis, infection, preeclampsia, and gestational diabetes (GDM). Additionally, reduced Treg levels were identified in preeclampsia, GDM, and pPROM as well as chorioamnionitis presenting with increased Treg dysfunctionality. Treg deficiencies may contribute to health issues in preterm newborns. Current sPTB treatments are limited, underscoring the potential of in utero therapies targeting inflammation, including T cell interventions. Future research aims to establish consensus on the role of Tregs in sPTB and associated conditions and advancing understanding of mechanisms leading to Treg deficiencies in adverse pregnancy outcomes.

KW - Humans

KW - Pregnancy

KW - T-Lymphocytes, Regulatory/immunology

KW - Female

KW - Premature Birth/immunology

KW - Pregnancy Outcome

KW - Immunomodulation

KW - Infant, Newborn

KW - Fetal Membranes, Premature Rupture/immunology

KW - Diabetes, Gestational/immunology

UR - http://www.scopus.com/inward/record.url?scp=85210552120&partnerID=8YFLogxK

U2 - 10.3390/ijms252211878

DO - 10.3390/ijms252211878

M3 - Review article

C2 - 39595948

SN - 1661-6596

VL - 25

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

IS - 22

M1 - 11878

ER -

The Immunomodulatory Role of Regulatory T Cells in Preterm Birth and Associated Pregnancy Outcomes

Abstract

Keywords

UN SDGs

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