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King's College London
Health

Regulatory T Cells in Pregnancy Adverse Outcomes (Rutepo)

Tregs, or regulatory T cells, are a type of immune cell that play a crucial role during pregnancy. These cells help regulate the immune responses in the maternal-fetal interface to protect the developing fetus from rejection by the mother's immune system.

During pregnancy, the immune system undergoes significant changes to create an environment favourable for the fetus's development and growth. Tregs are one of the main components of this immune adaptation, and they are primarily responsible for maintaining the immune tolerance towards fetal antigens.

Low levels of Tregs have been associated with pregnancy complications such as pre-eclampsia, recurrent pregnancy loss, and preterm birth. Studies have shown that boosting the number of Tregs during pregnancy can improve pregnancy outcomes and reduce the risk of complications.

Tregs during healthy pregnancy

Aims

We are currently investigating the various Treg subset and ways to manipulate Tregs to predict, prevent and treat pregnancy complications.

Methods

The Fetal Medicine Foundation at the Fetal Medicine Research Institute in Denmark Hill supports our study. Pregnant individuals attending routine appointments at King’s College Hospital are recruited. About 10% of pregnancies are affected by gestational diabetes, 3% with pre-eclampsia and 1.6% with preterm birth. We have a mixture of various demographics at the King's Health Partners NHS Trusts.

We are currently studying the differences in the immune cells in the cohorts who developed pregnancy adverse outcomes and more specifically, in Tregs, Th1, Th2 and Th17.

Impact

Tregs hold great potential as a predictive marker or therapeutic asset, identifiable early in pregnancy. Future studies could investigate strategies to modify these cells as a therapeutic approach in developing a personalised management plan.

Work that has informed Regulatory T Cells in Pregnancy Adverse Outcomes (Rutepo) includes:

  1. Giganti G, Atif M, Mohseni Y, et al. Treg cell therapy: How cell heterogeneity can make the difference. Eur J Immunol. 2021;51(1):39-55. doi:10.1002/eji.201948131
  2. Green S, Politis M, Rallis KS, et al. Regulatory T Cells in Pregnancy Adverse Outcomes: A Systematic Review and Meta-Analysis. Front Immunol. 2021;12(October):1-13. doi:10.3389/fimmu.2021.737862
  3. Gomez-Lopez N, Arenas-Hernandez M, Romero R, et al. Regulatory T Cells Play a Role in a Subset of Idiopathic Preterm Labor/Birth and Adverse Neonatal Outcomes. Cell Rep. 2020;32(1). doi:10.1016/j.celrep.2020.107874
  4. Schober L, Radnai D, Spratte J, et al. The role of regulatory T cell (Treg) subsets in gestational diabetes mellitus. Clin Exp Immunol. 2014;177(1):76-85. doi:10.1111/cei.12300
  5. Efthymiou A, Mureanu N, Pemberton R, et al. Isolation and freezing of human peripheral blood mononuclear cells from pregnant patients. STAR Protoc. 2022;3(1):101204. doi:10.1016/j.xpro.2022.101204
  6. Robertson SA, Green ES, Care AS, et al. Therapeutic potential of regulatory T cells in preeclampsia-opportunities and challenges. Front Immunol. 2019;10(MAR):1-18. doi:10.3389/fimmu.2019.00478
  7. Proschinger S, Winker M, Joisten N, Bloch W, Palmowski J, Zimmer P. The effect of exercise on regulatory T cells: A systematic review of human and animal studies with future perspectives and methodological recommendations. Exerc Immunol Rev. 2021;27(93):142-166. http://www.ncbi.nlm.nih.gov/pubmed/33965900
  8. van der Zalm IJB, van der Valk ES, Wester VL, et al. Obesity-associated T-cell and macrophage activation improve partly after a lifestyle intervention. Int J Obes. 2020;44(9):1838-1850. doi:10.1038/s41366-020-0615-6
  9. Papp G, Szabó K, Jámbor I, et al. Regular Exercise May Restore Certain Age-Related Alterations of Adaptive Immunity and Rebalance Immune Regulation. Front Immunol. 2021;12(April):1-13. doi:10.3389/fimmu.2021.639308
  10. Nechama M, Makayes Y, Resnick E, Meir K, Volovelsky O. Rapamycin and dexamethasone during pregnancy prevent tuberous sclerosis complex-associated cystic kidney disease. JCI insight. 2020;5(13):1-10. doi:10.1172/jci.insight.136857
  11. Furukawa A, Wisel SA, Tang Q. Impact of Immune-Modulatory Drugs on Regulatory T Cell. Transplantation. 2016;100(11):2288-2300. doi:10.1097/TP.0000000000001379
  12. Mohseni YR, Tung SL, Dudreuilh C, Lechler RI, Fruhwirth GO, Lombardi G. The Future of Regulatory T Cell Therapy: Promises and Challenges of Implementing CAR Technology. Front Immunol. 2020;11(July):1-13. doi:10.3389/fimmu.2020.01608
  13. Reading JL, Roobrouck VD, Hull CM, et al. Augmented Expansion of Treg Cells From Healthy and Autoimmune Subjects via Adult Progenitor Cell Co-Culture. Front Immunol. 2021;12(September):1-14. doi:10.3389/fimmu.2021.716606
  14. Mason GM, Lowe K, Melchiotti R, et al. Phenotypic Complexity of the Human Regulatory T Cell Compartment Revealed by Mass Cytometry. J Immunol. 2015;195(5):2030-2037. doi:10.4049/jimmunol.1500703

Work that has informed Regulatory T Cells in Pregnancy Adverse Outcomes (Rutepo) includes:

  1. Giganti G, Atif M, Mohseni Y, et al. Treg cell therapy: How cell heterogeneity can make the difference. Eur J Immunol. 2021;51(1):39-55. doi:10.1002/eji.201948131
  2. Green S, Politis M, Rallis KS, et al. Regulatory T Cells in Pregnancy Adverse Outcomes: A Systematic Review and Meta-Analysis. Front Immunol. 2021;12(October):1-13. doi:10.3389/fimmu.2021.737862
  3. Gomez-Lopez N, Arenas-Hernandez M, Romero R, et al. Regulatory T Cells Play a Role in a Subset of Idiopathic Preterm Labor/Birth and Adverse Neonatal Outcomes. Cell Rep. 2020;32(1). doi:10.1016/j.celrep.2020.107874
  4. Schober L, Radnai D, Spratte J, et al. The role of regulatory T cell (Treg) subsets in gestational diabetes mellitus. Clin Exp Immunol. 2014;177(1):76-85. doi:10.1111/cei.12300
  5. Efthymiou A, Mureanu N, Pemberton R, et al. Isolation and freezing of human peripheral blood mononuclear cells from pregnant patients. STAR Protoc. 2022;3(1):101204. doi:10.1016/j.xpro.2022.101204
  6. Robertson SA, Green ES, Care AS, et al. Therapeutic potential of regulatory T cells in preeclampsia-opportunities and challenges. Front Immunol. 2019;10(MAR):1-18. doi:10.3389/fimmu.2019.00478
  7. Proschinger S, Winker M, Joisten N, Bloch W, Palmowski J, Zimmer P. The effect of exercise on regulatory T cells: A systematic review of human and animal studies with future perspectives and methodological recommendations. Exerc Immunol Rev. 2021;27(93):142-166. http://www.ncbi.nlm.nih.gov/pubmed/33965900
  8. van der Zalm IJB, van der Valk ES, Wester VL, et al. Obesity-associated T-cell and macrophage activation improve partly after a lifestyle intervention. Int J Obes. 2020;44(9):1838-1850. doi:10.1038/s41366-020-0615-6
  9. Papp G, Szabó K, Jámbor I, et al. Regular Exercise May Restore Certain Age-Related Alterations of Adaptive Immunity and Rebalance Immune Regulation. Front Immunol. 2021;12(April):1-13. doi:10.3389/fimmu.2021.639308
  10. Nechama M, Makayes Y, Resnick E, Meir K, Volovelsky O. Rapamycin and dexamethasone during pregnancy prevent tuberous sclerosis complex-associated cystic kidney disease. JCI insight. 2020;5(13):1-10. doi:10.1172/jci.insight.136857
  11. Furukawa A, Wisel SA, Tang Q. Impact of Immune-Modulatory Drugs on Regulatory T Cell. Transplantation. 2016;100(11):2288-2300. doi:10.1097/TP.0000000000001379
  12. Mohseni YR, Tung SL, Dudreuilh C, Lechler RI, Fruhwirth GO, Lombardi G. The Future of Regulatory T Cell Therapy: Promises and Challenges of Implementing CAR Technology. Front Immunol. 2020;11(July):1-13. doi:10.3389/fimmu.2020.01608
  13. Reading JL, Roobrouck VD, Hull CM, et al. Augmented Expansion of Treg Cells From Healthy and Autoimmune Subjects via Adult Progenitor Cell Co-Culture. Front Immunol. 2021;12(September):1-14. doi:10.3389/fimmu.2021.716606
  14. Mason GM, Lowe K, Melchiotti R, et al. Phenotypic Complexity of the Human Regulatory T Cell Compartment Revealed by Mass Cytometry. J Immunol. 2015;195(5):2030-2037. doi:10.4049/jimmunol.1500703
Project status: Ongoing

Principal Investigators

Investigators

Funding

Funding Body: Fetal Medicine Foundation

Amount: £530625

Period: February 2021 - January 2028

Contact us

panicos.shangaris@kcl.ac.uk