A1 Refereed original research article in a scientific journal
GPR55 in B cells limits atherosclerosis development and regulates plasma cell maturation
Authors: 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
Publisher: Springer Nature
Publication year: 2022
Journal: Nature cardiovascular research
Journal name in source: Nature cardiovascular research
Journal acronym: Nat Cardiovasc Res
Volume: 1
First page : 1056
Last page: 1071
ISSN: 2731-0590
eISSN: 2731-0590
DOI: https://doi.org/10.1038/s44161-022-00155-0
Web address : https://doi.org/10.1038/s44161-022-00155-0
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/177916761
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 (PC), 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 immunoglobulin (Ig)G 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.
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