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: Professor Ye Htun Oo, University of Birmingham, UK
- Second opponent: Professor Susanna Cardell, University of Gothenburg, Sweden
- Third member and chair of the evaluation committee: Professor Jan Terje Andersen, University of Oslo
Chair of the Defence
Professor II Terje Rootwelt-Revheim, University of Oslo
Principal Supervisor
Researcher Espen Melum, University of Oslo
Summary
The etiology and pathophysiology of cholangiopathies are mostly unknown and their disease courses are often chronic and progressive due to limited treatment options. The biliary anatomy limits the accessibility to the bile ducts in experimental models and complicates study of biliary immunopathology. The purpose of this thesis was to study the regulatory mechanisms in biliary inflammation, with an emphasis on the role of natural killer T (NKT) cells and the role of lipid antigen presentation in the bile ducts.
We first established a novel bile duct injection model in mice to access the bile ducts for in vivo study of biliary immunopathology. This model may be valuable in future studies of normal biliary physiology and different pathophysiological disease mechanisms as it was well tolerated and easily reproducible.
NKT cells are activated by lipid antigen presentation by the CD1d-molecule. Cholangiocytes function as antigen presenting cells (APCs) with CD1d-dependent activation of NKT cells in vitro and we hypothesized that this immunoregulatory pathway is important in the bile ducts. To explore this, we first demonstrated that intrabiliary injection of the NKT cell-activating agent oxazolone in wild type mice caused an acute cholangitis with activation of NKT cells. Cd1d-/- mice that lack NKT cells and wild type mice pretreated with antibody blocking of CD1d were protected from disease. These findings implicate that cells in the bile ducts function as APCs in vivo and activate NKT cells in a CD1d-restricted manner.
Finally, we demonstrated the presence of NKT cell-activating antigens in bile from patients with various liver diseases. This may be of importance in biliary immunopathology.
As NKT cells are potent immunomodulators that can act both protective and detrimental in disease, future studies should aim to elucidate this biliary immune pathway as it may expose potentially new therapeutic approaches in cholangiopathies.
Additional information
Contact the research support staff.