Regulatory Immune Responses and Repair Mechanisms in Atherosclerosis
Author
Summary, in English
The first part of this thesis investigates the role of regulatory immune responses targeting plaque-related antigens. In paper I, we developed a matrigel-based method to characterize T helper 2 immune responses against human apolipoprotein B100 (ApoB100). We report that matrigel loaded with the antigen of interest can be used to measure antigen-specific immune cell accumulation and cytokine production. In paper II, we report that B cells pulsed with peptide 210 (p210) from ApoB100 coupled to the cholera toxin B subunit (p210-CTB) acquire a regulatory phenotype and induce Tregs in vivo. In the third paper, we unexpectedly found increased frequencies of circulating regulatory T cells in patients with prevalent cardiovascular disease. Our results indicate that the general immune cell activation in patients with prevalent cardiovascular disease can cause a compensatory increase in regulatory T cells to counteract the immune response.
In the second part of this thesis, we focused on the role of smooth muscle cells in atherosclerosis. In paper IV, we show that IL-22 is involved in controlling smooth muscle cell phenotype. More specifically, IL-22 deficient atherosclerotic mice develop smaller plaques with increased expression of contractile proteins. Increased numbers of smooth muscle cells remaining in a contractile phenotype in the media and decreased collagen content in the plaques could possibly contribute to the smaller plaque size observed in IL-22 deficient mice. Finally, in paper V, we present data suggesting that high levels of smooth muscle cell growth factors (platelet-derived growth factor, epidermal growth factor, heparin-binding epidermal growth factor) measured in plasma can reflect a fibrous plaque phenotype. In particular, high plasma levels of heparin-binding epidermal growth factor at baseline was associated with a decreased risk for developing a coronary event.
Department/s
Publishing year
2015
Language
English
Publication/Series
Lund University Faculty of Medicine Doctoral Dissertation Series
Volume
2015:12
Full text
Document type
Dissertation
Publisher
Experimental Cardiovascular Research Unit, Lund University
Topic
- Cardiac and Cardiovascular Systems
Keywords
- Atherosclerosis
- Cardiovascular disease
- T helper 2 cells
- ApoB100
- Regulatory B cells
- Regulatory T cells
- Smooth muscle cells
- IL-22.
Status
Published
Research group
- Cardiovascular Research - Immunity and Atherosclerosis
Supervisor
- Jan Nilsson
- Gunilla Nordin Fredrikson
- Harry Björkbacka
- Maria Wigren
ISBN/ISSN/Other
- ISSN: 1652-8220
- ISBN: 978-91-7619-092-0
Defence date
6 February 2015
Defence time
09:00
Defence place
Kvinnoklinikens Aula, Skåne University Hospital, Malmö
Opponent
- Esther Lutgens