The public defence will be held as a video conference over Zoom.
The defence will follow regular procedure as far as possible, hence it will be open to the public and the audience can ask ex auditorio questions when invited to do so.
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Due to copyright reasons, an electronic copy of the thesis must be ordered from the faculty. In order for the faculty to have time to process the order, it must be received by the faculty no later than 2 days prior to the public defence. Orders received later than 2 days before the defence will not be processed. Inquiries regarding the thesis after the public defence must be addressed to the candidate.
Digital Trial Lecture - time and place
Adjudication committee
- First opponent: Assistant Professor Lara Kular, Karolinska Institutet, Stockholm
- Second opponent: Professor Pål Sætrom, Norwegian University of Science and Technology, Trondheim
- Third member and chair of the evaliuation committee: Researcher Espen Melum, Institute of Clinical Medicine, University of Oslo
Chair of defence
Professor II Mona Kristiansen Beyer, Institute of Clinical Medicine, University of Oslo
Principal Supervisor
Researcher Steffan D. Bos, Institute of Clinial Medicine, University of Oslo
Summary
Genome-wide association studies of the complex disease multiple sclerosis (MS) have found 233 genetic variants associated with the disease that only explains part of the heritability. The epigenetic factor DNA methylation might account for a part of the remaining MS heritability, and link environmental exposures to disease. Furthermore, expression of genes might point to candidate genes and pathways relevant for MS. In this thesis, genome-wide DNA methylation and gene expression have been quantified to study the characteristics of immune cells, aiming to unravel molecular mechanisms and candidate genes underlying the disease.
CD4+ and CD8+ T cells are important components of the adaptive immune system and evidence indicates that they are central in MS pathology. The onset of MS is likely the result of a complex interplay between genetic and environmental factors.
This doctoral thesis provides evidence of differences in the DNA methylation profile of CD4+ and CD8+ T cells isolated from MS patients compared to healthy controls in specific genomic regions. Furthermore, we provide evidence of a more active gene expression profile in CD8+ T cells from MS patients. Among the differentially expressed genes in CD8+ T cells between MS and healthy controls, there is an overrepresentation of genes with MS genetic variants. Additionally, this thesis is the first to provide evidence for a disease-duration related difference in DNA methylation levels in treated and untreated MS patients. Untreated MS patients show more abundant differences in DNA methylation at the time of follow-up, compared to treated MS patients at the time of follow-up.
The present study has contributed with molecular characterization of CD4+ and CD8+ T cells in MS and provides new evidence for the involvement of these cells in the disease pathology.
Additional information
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