GPR55 in B cells limits atherosclerosis development and regulates plasma cell maturation

Guillamat-Prats, Raquel; Hering, Daniel; Derle, Abhishek; Rami, Martina; Haerdtner, 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 und Steffens, Sabine (2022): GPR55 in B cells limits atherosclerosis development and regulates plasma cell maturation. In: Nature Cardiovascular Research, Bd. 1, Nr. 11: 1056-+

Abstract

Dissecting the pathways regulating the adaptive immune response in atherosclerosis is of particular therapeutic interest. Here we report that the lipid G-protein-coupled receptor GPR55 is highly expressed by splenic plasma cells (PCs), upregulated in mouse spleens during atherogenesis and human unstable or ruptured compared to stable plaques. Gpr55-deficient mice developed larger atherosclerotic plaques with increased necrotic core size compared to their corresponding controls. Lack of GPR55 hyperactivated B cells, disturbed PC maturation and resulted in IgG overproduction. B-cell-specific Gpr55 depletion or adoptive transfer of Gpr55-deficient B cells was sufficient to promote plaque development and elevated IgG titers. In vitro, the endogenous GPR55 ligand lysophsophatidylinositol (LPI) enhanced PC proliferation, whereas GPR55 antagonism blocked PC maturation and increased their mitochondrial content. Collectively, these discoveries provide previously undefined evidence for GPR55 in B cells as a key modulator of the adaptive immune response in atherosclerosis. Using various mouse models, human plaque data and isolated B cells combined with state-of-the-art imaging and transcriptomic analysis, the authors show that the G-protein-coupled orphan receptor GPR55 regulates B cell activation and plasma cell differentiation during hypercholesterolemia, which crucially affects atherosclerosis.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin > Munich Cluster for Systems Neurology (SyNergy)
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Sprache: Englisch
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198