Depletion of B2 but not B1a B cells in BAFF receptor-deficient ApoE mice attenuates atherosclerosis by potently ameliorating arterial inflammation
| Autor: | Tin Kyaw, Christopher Tay, Ban-Hock Toh, Tahlia Gadowski, Peter G. Tipping, Peter Kanellakis, Fabeinne MacKay, Hamid Hosseini, Alex Bobik |
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| Rok vydání: | 2011 |
| Předmět: |
Male
medicine.medical_specialty Chemokine Endothelium Science T cell Immune Cells Immunology Down-Regulation Inflammation Cardiovascular Proinflammatory cytokine Mice Apolipoproteins E Model Organisms Internal medicine medicine Cytotoxic T cell Macrophage Animals Biology Chemokine CCL2 Mice Knockout Arteritis Multidisciplinary biology Immunity Endothelial Cells Arteries Animal Models Atherosclerosis Mice Inbred C57BL medicine.anatomical_structure Endocrinology Gene Expression Regulation Cytoprotection biology.protein Cytokines Medicine Clinical Immunology medicine.symptom Inflammation Mediators CD8 B-Cell Activation Factor Receptor Research Article |
| Zdroj: | PLoS ONE PLoS ONE, Vol 7, Iss 1, p e29371 (2012) |
| ISSN: | 1932-6203 |
| Popis: | We have recently identified conventional B2 cells as atherogenic and B1a cells as atheroprotective in hypercholesterolemic ApoE(-/-) mice. Here, we examined the development of atherosclerosis in BAFF-R deficient ApoE(-/-) mice because B2 cells but not B1a cells are selectively depleted in BAFF-R deficient mice. We fed BAFF-R(-/-) ApoE(-/-) (BaffR.ApoE DKO) and BAFF-R(+/+)ApoE(-/-) (ApoE KO) mice a high fat diet (HFD) for 8-weeks. B2 cells were significantly reduced by 82%, 81%, 94%, 72% in blood, peritoneal fluid, spleen and peripheral lymph nodes respectively; while B1a cells and non-B lymphocytes were unaffected. Aortic atherosclerotic lesions assessed by oil red-O stained-lipid accumulation and CD68+ macrophage accumulation were decreased by 44% and 50% respectively. B cells were absent in atherosclerotic lesions of BaffR.ApoE DKO mice as were IgG1 and IgG2a immunoglobulins produced by B2 cells, despite low but measurable numbers of B2 cells and IgG1 and IgG2a immunoglobulin concentrations in plasma. Plasma IgM and IgM deposits in atherosclerotic lesions were also reduced. BAFF-R deficiency in ApoE(-/-) mice was also associated with a reduced expression of VCAM-1 and fewer macrophages, dendritic cells, CD4+ and CD8+ T cell infiltrates and PCNA+ cells in lesions. The expression of proinflammatory cytokines, TNF-α, IL1-β and proinflammatory chemokine MCP-1 was also reduced. Body weight and plasma cholesterols were unaffected in BaffR.ApoE DKO mice. Our data indicate that B2 cells are important contributors to the development of atherosclerosis and that targeting the BAFF-R to specifically reduce atherogenic B2 cell numbers while preserving atheroprotective B1a cell numbers may be a potential therapeutic strategy to reduce atherosclerosis by potently reducing arterial inflammation. |
| Databáze: | OpenAIRE |
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