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 Marvin M. Van Luijn, Erasmus University Medical Center, The Netherlands
- Second opponent: Post doc Emanuela Pasciuto, KU Leuven, Belgium
- Third member and chair of the evaluation committee: Associate Professor Andreas Lossius, Institute of Clinical Medicine, University of Oslo
Chair of defence
Associate Professor Johanne Egge Rinholm, Institute of Basic Medical Sciences, University of Oslo
Principal supervisor
Tone Berge, Oslo University Hospital
Summary
The underlying cause of multiple sclerosis (MS) is unknown, but genome-wide association studies have identified 233 genetic variations associated with increased risk of MS. T cells are an important part of the immune system, and several lines of evidence indicate that these cells also play a central role for MS development.
The aim of this thesis were to unravel molecular mechanisms leading to development of MS. T cell processes were studied to identify the functional contribution of genetic risk variants for MS and to identify pathological pathways.
Both CLEC16A and DEXI are MS-susceptibility genes and their expression in immune cells have been shown to correlate with carrying risk alleles of MS-associated genetic variants. Functional studies of CLEC16A and DEXI in T cells were conducted to understand their potential contribution into MS development. CLEC16A was found to localize in rapid recycling endosomes and had an impact on receptor recycling. DEXI was found to move to the cell nucleus upon T cell activation. More studies are required to understand the exact role of CLEC16A and DEXI in T cell processes. However, the functions found in the present study, indicate that dysregulation of both genes individually could affect the immune response.
By a proteomic approach, CD4+ T cell from patients with MS were compared with cells from healthy controls. The cells from patients showed higher expression of proteins involved in T cell activation signaling. Further, by stimulating the CD4+ T cells of the different groups equally, different cellular pathways were regulated in the two groups. This emphasizes that T cell activation is affected in MS.
Additional information
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