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The role of regulatory T-cells (Tregs) in pregnancy, pre-eclampsia and beyond

Miedema A, (2016) The role of regulatory T-cells (Tregs) in pregnancy, pre-eclampsia and beyond. Master's Thesis / Essay, Biomedical Sciences.

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Abstract

This review is about regulatory T-cells (Tregs) during pregnancy, pregnancy complications and their application against transplant rejection. Tregs can be identified based on the expression of CD4, CD25 and the FOXP3 transcription factor. These cells can be formed within the thymus or within the periphery from naïve T-cells. Tregs use a diverse set of mechanisms to cause immunosuppression and maternal fetal-tolerance. For example inhibition of other T-cell subsets (Th17 and Th1) and the production of anti-inflammatory cytokines (IL-10, TGF-β and IL-35). For a successful pregnancy an increase in Tregs is essential. No increase in Tregs or impaired increase will lead to miscarriage or severe pregnancy complications such as preeclampsia (PE), because Tregs play an important role in creating a tolerant state against the semi-allogenic fetus. Maintenance of maternal fetal tolerance is probably regulated by PDL1 signalling. Many animal and human studies are performed about Tregs in healthy pregnancies and in PE. Sometimes results are controversial. However, most studies show a local/peripheral increase in Tregs during healthy pregnancy and a local/peripheral decrease in Tregs during PE pathology. Mechanisms how a lack of Tregs contributes to PE pathology include impaired trophoblast invasion/incomplete spiral artery remodelling, failure of maternal fetal tolerance and an imbalance in anti- and pro- inflammatory cytokines resulting in inflammation. Chronic inflammation in PE causes endothelial dysfunction contributing to the main symptom of PE: high blood pressure. At the moment there is still no treatment for PE, besides delivery. Therefore, it should be useful to develop Treg based immunotherapy for PE in the future to restore immune homeostasis. In a rat model of PE (RUPP) expansion of Tregs during pregnancy is able to reduce blood pressure. Moreover clinical trials are running at the moment to examine the efficacy of Treg immunotherapy against transplant rejection.

Item Type: Thesis (Master's Thesis / Essay)
Degree programme: Biomedical Sciences
Thesis type: Master's Thesis / Essay
Language: English
Date Deposited: 15 Feb 2018 08:24
Last Modified: 15 Feb 2018 08:24
URI: http://fse.studenttheses.ub.rug.nl/id/eprint/14474

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