B cell modulation in atherosclerosis

Douna, H. (2019)

Doctoral Thesis

Cardiovascular disease is a major global burden and atherosclerosis is the main underlying pathological process. Despite better management of cholesterol levels, there remains a significant residual risk of developing atherosclerosis and cardiovascular events. Hence, novel pathways and targets should be identified to optimize atherosclerosis therapy. Despite dyslipidemia, the immune system is also heavily involved in the pathophysiology of atherosclerosis. Protective immune responses in the acute setting of increased cholesterol levels eventually turn into debilitating responses when the immune system is chronically stimulated. Hence, we aimed to identify new therapeutic targets to dampen the immune response in atherosclerosis. More specifically, we focused our efforts on modulating the B lymphocyte response, for which there was a scarcity of data. In this thesis we describe novel ways to modulate the B cell response in atherosclerosis. We have found that there are specific B cell subsets that have different effects on the progress of atherosclerosis. For instance, removal of TIM-1+ B cells resulted in increased atherosclerosis, while removal of BTLA+ follicular B cells reduced atherosclerosis. In conclusion, this thesis provides promising immunological targets for the treatment of atherosclerosis.

• Atherosclerosis
• Inflammation
• Lymphocytes
• B cells
• BTLA
• TIM-1
• IL10
• PD-L1

• All authors: Douna, H.
• Supervisor: Kuiper, J.
• Co-supervisor: Foks, A.C.; Puijvelde, G.H.M. van
• Committee: Irth, H.; Bouwstra, J.A.; Lutgens, E.; Quax, P.H.A.; Binder, C.J.
• Qualification: Doctor (dr.)
• Awarding Institution: Leiden Academic Centre for Drugs Research (LACDR), Faculty of Science, Leiden University
• Date: 2019-06-06
• ISBN (print): 9789463612746