Marshall, Lucy Rachel;
(2024)
Novel mechanistic insights into the role of T cells in the pathogenesis of Juvenile Dermatomyositis.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
T cells which are polarised towards a Th1 functional signature play an important role within the human immune system by stimulating immune responses via secretion of cytokines such as IFN-γ. Th1 cells are entwined with several other processes that make up human immunology which when working properly results in a healthy immune system. Juvenile Dermatomyositis (JDM) is a rare autoimmune paediatric disease which is heterogeneous in nature and whose underlying immunopathogenesis, whereby the immune system makes responses against self tissues, like other autoimmune diseases is not fully understood. The aim of this thesis was to investigate the function and signature of Th1 cells in the disease JDM. Doing so could lead to an enhanced understanding of the immune system in autoimmunity in general or JDM in particular to instruct future research into treatment targets. Results of multiple stimulatory assays demonstrated a reduced Th1 response via decreased levels of IFN-γ from Th1 cells within the blood of JDM patients compared to healthy age- and sexmatched controls. Further investigation shows this apparent reduction in frequency of Th1 cells in JDM was not due to an under-representation of Th1 cells at baseline, overrepresentation of other Th subsets such as Th17, TfH or Treg cells nor a defect in cell proliferation. Other initial lines of investigation including patient serum cytokine levels that could decrease Th1 production and glucose transporter abilities of CD4+ T cells also could not explain these results. Further work tested transcriptional signature of CD4+ cells from JDM in relation to Th subpopulations, and compared in vitro data against clinical phenotypes. The data within this thesis have used a wide range of approaches to dissect Th1 biology in JDM and analysed their implications within the clinical data of the same patients. This also provides a basis for further work focusing on JDM Th1 biology and potential therapeutics.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Novel mechanistic insights into the role of T cells in the pathogenesis of Juvenile Dermatomyositis |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2022. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| Keywords: | Juvenile Dermatomyositis, T cells, autoimmune, immunology, CD4 |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10186815 |
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