TY - JOUR
T1 - GPR55 in B cells limits atherosclerosis development and regulates plasma cell maturation
AU - Guillamat-Prats, Raquel
AU - Hering, Daniel
AU - Derle, Abhishek
AU - Rami, Martina
AU - Härdtner, Carmen
AU - Santovito, Donato
AU - Rinne, Petteri
AU - Bindila, Laura
AU - Hristov, Michael
AU - Pagano, Sabrina
AU - Vuilleumier, Nicolas
AU - Schmid, Sofie
AU - Janjic, Aleksandar
AU - Enard, Wolfgang
AU - Weber, Christian
AU - Maegdefessel, Lars
AU - Faussner, Alexander
AU - Hilgendorf, Ingo
AU - Steffens, Sabine
PY - 2022/11
Y1 - 2022/11
N2 - 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.
AB - 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.
U2 - 10.1038/s44161-022-00155-0
DO - 10.1038/s44161-022-00155-0
M3 - Article
C2 - 36523570
SN - 2731-0590
VL - 1
SP - 1056
EP - 1071
JO - Nature cardiovascular research
JF - Nature cardiovascular research
IS - 11
ER -