Role of orphan receptor GPR55 in immune cell homeostasis and atherosclerosis
Final Report Abstract
Immune mechanisms are crucially involved in the pathogenesis of atherosclerosis and its clinical manifestations. Mounting evidence demonstrates a role of B cells and humoral immunity in atherosclerotic cardiovascular disease, which is supported by elevated titers of disease-specific antibodies (against antigens derived from modified lipoproteins, such as oxidation-specific epitopes). B cells mediate both protective and detrimental effects in cardiovascular disease, as they can secrete antibodies with both pro-atherogenic and anti-atherogenic effects. Current research efforts aim to gain an improved understanding of how B cells influence atherosclerotic disease, with the ultimate goal to develop novel B cell-targeted therapies for this life-threatening disease. In this context, we studied the immunomodulatory role of GPR55, a G-protein coupled receptor that is activated by endogenous lipid mediators. Our findings in experimental mouse models of atherosclerosis and human plaques indicate that GRP55 signaling is important for limiting B cell activation and humoral responses during hypercholesterolemia, suggesting that GPR55 signaling has an atheroprotective role.
Publications
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Endocannabinoid Signalling in Atherosclerosis and Related Metabolic Complications. Thrombosis and Haemostasis, 119(04), 567-575.
Guillamat-Prats, Raquel; Rami, Martina; Herzig, Stephan & Steffens, Sabine
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Immunotherapy for cardiovascular disease. European Heart Journal, 40(48), 3937-3946.
Lutgens, Esther; Atzler, Dorothee; Döring, Yvonne; Duchene, Johan; Steffens, Sabine & Weber, Christian
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GPR55 in B cells limits atherosclerosis development and regulates plasma cell maturation. Nature Cardiovascular Research, 1(11), 1056-1071.
Guillamat-Prats, Raquel; Hering, Daniel; Derle, Abhishek; Rami, Martina; Härdtner, Carmen; Santovito, Donato; Rinne, Petteri; Bindila, Laura; Hristov, Michael; Pagano, Sabrina; Vuilleumier, Nicolas; Schmid, Sofie; Janjic, Aleksandar; Enard, Wolfgang; Weber, Christian; Maegdefessel, Lars; Faussner, Alexander; Hilgendorf, Ingo & Steffens, Sabine
