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... Show moreCardiovascular 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. Show less
Parasitic helminths modulate host immune responses. While the induction of type 2 immune responses is a widely recognized feature of helminth infections, a network of regulatory immune responses is... Show moreParasitic helminths modulate host immune responses. While the induction of type 2 immune responses is a widely recognized feature of helminth infections, a network of regulatory immune responses is often dominant during the chronic phase of infection. Suppression of the host immune system during helminth infections inhibits anti-parasite immunity, prevents tissue damage due to excessive inflammation and conveys spill-over suppression to inflammatory conditions such as allergy and asthma. The first part of this thesis focuses on the role of regulatory B cells, a prominent member of the immune regulatory network, in protection from allergic asthma by chronic Schistosoma (S.) mansoni infections. It furthermore identifies signals required for schistosome-induced regulatory B cell development. The second part of this thesis describes the protective effect of S. mansoni eggs, and a specific egg-derived glycoprotein, against allergic asthma in the absence of chronic infection. A better understanding how helminthes including S. mansoni modulate host immune responses, and the implications this has for inflammatory diseases such as allergic asthma, may provide valuable leads for the development of novel pharmaceutical agents for the treatment of allergic disorders. Show less
