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

Raquel Guillamat-Prats; Daniel Hering; Abhishek Derle; Martina Rami; Carmen Härdtner; Donato Santovito; Petteri Rinne; Laura Bindila; Michael Hristov; Sabrina Pagano; Nicolas Vuilleumier; Sofie Schmid; Aleksandar Janjic; Wolfgang Enard; Christian Weber; Lars Maegdefessel; Alexander Faussner; Ingo Hilgendorf; Sabine Steffens

doi:10.1038/s44161-022-00155-0

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

Raquel Guillamat-Prats, Daniel Hering, Abhishek Derle, Martina Rami, Carmen Härdtner, Donato Santovito, Petteri Rinne, Laura Bindila, Michael Hristov, Sabrina Pagano, Nicolas Vuilleumier, Sofie Schmid, Aleksandar Janjic, Wolfgang Enard, Christian Weber, Lars Maegdefessel, Alexander Faussner, Ingo Hilgendorf, Sabine Steffens^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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 (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.

Original language	English
Pages (from-to)	1056-1071
Number of pages	16
Journal	Nature cardiovascular research
Volume	1
DOIs	https://doi.org/10.1038/s44161-022-00155-0
Publication status	Published - Nov 2022

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Cite this

Guillamat-Prats, R., Hering, D., Derle, A., Rami, M., Härdtner, C., Santovito, D., Rinne, P., Bindila, L., Hristov, M., Pagano, S., Vuilleumier, N., Schmid, S., Janjic, A., Enard, W., Weber, C., Maegdefessel, L., Faussner, A., Hilgendorf, I., & Steffens, S. (2022). GPR55 in B cells limits atherosclerosis development and regulates plasma cell maturation. Nature cardiovascular research, 1, 1056-1071. https://doi.org/10.1038/s44161-022-00155-0

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title = "GPR55 in B cells limits atherosclerosis development and regulates plasma cell maturation",

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 (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.",

author = "Raquel Guillamat-Prats and Daniel Hering and Abhishek Derle and Martina Rami and Carmen H{\"a}rdtner and Donato Santovito and Petteri Rinne and Laura Bindila and Michael Hristov and Sabrina Pagano and Nicolas Vuilleumier and Sofie Schmid and Aleksandar Janjic and Wolfgang Enard and Christian Weber and Lars Maegdefessel and Alexander Faussner and Ingo Hilgendorf and Sabine Steffens",

year = "2022",

month = nov,

doi = "10.1038/s44161-022-00155-0",

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Guillamat-Prats, R, Hering, D, Derle, A, Rami, M, Härdtner, C, Santovito, D, Rinne, P, Bindila, L, Hristov, M, Pagano, S, Vuilleumier, N, Schmid, S, Janjic, A, Enard, W, Weber, C, Maegdefessel, L, Faussner, A, Hilgendorf, I & Steffens, S 2022, 'GPR55 in B cells limits atherosclerosis development and regulates plasma cell maturation', Nature cardiovascular research, vol. 1, pp. 1056-1071. https://doi.org/10.1038/s44161-022-00155-0

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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

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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.

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