|Title:||The role of interleukin 10 in immune tolerance – lessons learnt from human pregnancy|
|Authors:||Hsu, Peter Shang-Yu|
regulatory T cells
|Publisher:||University of Sydney.|
Faculty of Medicine.
Paediatrics & Child Health.
Children's Hospital at Westmead Clinical School.
|Abstract:||Pregnancy requires that the maternal immune system tolerates the semi-allogeneic fetus and therefore represents an important model for the study of human immune tolerance. The current thesis explores the immunological processes during pregnancy, focusing specifically on innate and adaptive immune interactions at the fetal-maternal interface and the transplacental regulation of maternal and fetal immunity. A unique population of DC-SIGN+ decidual antigen presenting cells (APCs) was identified, which efficiently induces Foxp3+ regulatory T (Treg) cells and CD4+HLA-G+ suppressive T cells. This process was shown to be defective in pre-eclampsia, in which a reduction of both induced Treg cells and CD4+HLA-G+ suppressive T cells was demonstrated. This immune tolerance breakdown likely contributes to the pathogenesis of pre-eclampsia. Interleukin 10 (IL-10) was identified as an important mediator of this fetal-maternal immune tolerance, where it was shown to tolerize APCs, upregulate HLA-G expression and potentiate the induction of suppressive human Treg cells from naïve CD4+ T cells. The later process was dependent on IL-10 mediated STAT3 signaling and preservation of Foxo1 function. Furthermore, IL-10 was shown to specifically upregulate Bcl2 expression in Treg cells, endowing them with a survival advantage. This was thought to be one of the mechanisms behind the alignment of Treg cells between the mother and the fetus, which represents the first evidence of transplacental regulation of cellular immunity, with significant implications for the field of transplacental immune programming. In summary, the current thesis presents evidence that IL-10 plays a central role in the immunological processes of human pregnancy, facilitating immune tolerance at the fetal-maternal interface and transplacental immune programming.|
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|Rights and Permissions:||The author retains copyright of this thesis. It may only be used for the purposes of research and study. It must not be used for any other purposes and may not be transmitted or shared with others without prior permission.|
|Type of Work:||PhD Doctorate|
|Type of Publication:||Doctor of Philosophy Ph.D.|
|Appears in Collections:||Sydney Digital Theses (University of Sydney Access only)|
|HSU Peter - Final thesis 1.pdf||Thesis||17.78 MB||Adobe PDF|
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