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May 27, 2019

87th EAS Congress

05 - GLOBAL AND HAEMATOPOIETIC CD22 DEFICIENCY IN LDLR-/- MICE REDUCE PLASMA TRIGLYCERIDE AND CHOLESTEROL LEVELS WITHOUT AFFECTING LESION FORMATION

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Atherosclerosis

Immunity

B cells

Lipid metabolism

Abstract

Abstract

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Keywords

Atherosclerosis

Immunity

B cells

Lipid metabolism

Abstract

Aim: Different B cell subsets and their effector functions have distinct roles in modulating atherosclerosis. CD22 is a B-cell specific co-receptor and a key regulator of B cell receptor (BCR) signalling that contributes to the fine-tuning of B cell activity and B cell fate. Our aim was to elucidate the role of CD22 in atherosclerosis. Method: Cd22-/-Ldlr-/- and Cd22+/+Ldlr-/- littermates were fed an atherogenic diet for 8 weeks. Additionally, Ldlr-/- mice were lethally irradiated and received bone marrow from Cd22-/- or Cd22+/+ mice followed by atherogenic diet for 10 weeks. Results: Cd22-/-Ldlr-/- mice displayed significant decreases in the number of marginal zone and B-1 cells compared to controls. In contrast, Ldlr-/- mice that received CD22-deficient bone marrow showed significant increases in these populations. Other splenic immune cell populations were unaffected in both models. Both mice deficient in global and haematopoietic CD22 displayed selective reductions in Th1-dependent IgG2c antibodies, which was mirrored in IgGs against CuOxLDL. Unexpectedly, mice that received CD22-deficient bone marrow developed significantly less diet-induced hypertriglyceridemia (465.5±75.1 vs 608.3±121.2mg/dl, p<0.0011), while Cd22-/-Ldlr-/- mice had reduced hypertriglyceridemia and hypercholesterolemia (371.3±97.2 vs 531.5±99.0 mg/dl, p=0.017, and 741.7±237.4 vs 1100±267.6 vs mg/dl, p=0.0689, respectively). Hepatic triglyceride and cholesterol levels and expression of cholesterol and triglyceride synthesis genes were not different. Despite differences in plasma lipid levels, neither global nor haematopoietic CD22 deficiency was found to have an effect on lesion size. Conclusion: Our data show a novel link between CD22 deficiency and plasma triglyceride and cholesterol levels that suggest a role for B cells in lipid metabolism.

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© Copyright 2019 Morressier GmbH.
All rights reserved.