| First Author | Tay C | Year | 2016 |
| Journal | Cardiovasc Res | Volume | 111 |
| Issue | 4 | Pages | 385-97 |
| PubMed ID | 27492217 | Mgi Jnum | J:253297 |
| Mgi Id | MGI:6107820 | Doi | 10.1093/cvr/cvw186 |
| Citation | Tay C, et al. (2016) B-cell-specific depletion of tumour necrosis factor alpha inhibits atherosclerosis development and plaque vulnerability to rupture by reducing cell death and inflammation. Cardiovasc Res 111(4):385-97 |
| abstractText | AIMS: B2 lymphocytes promote atherosclerosis development but their mechanisms of action are unknown. Here, we investigated the role of tumour necrosis factor alpha (TNF-alpha) produced by B2 cells in atherogenesis. METHODS AND RESULTS: We found that 50% of TNF-alpha-producing spleen lymphocytes were B2 cells and approximately 20% of spleen and aortic B cells produced TNF-alpha in hyperlipidemic ApoE(-/-) mice. We generated mixed bone marrow (80% muMT/20% TNF-alpha(-/-)) chimeric LDLR(-/-) mice where only B cells did not express TNF-alpha. Atherosclerosis was reduced in chimeric LDLR(-/-) mice with TNF-alpha-deficient B cells. TNF-alpha expression in atherosclerotic lesions and in macrophages were also reduced accompanied by fewer apoptotic cells, reduced necrotic cores, and reduced lesion Fas, interleukin-1beta and MCP-1 in mice with TNF-alpha-deficient B cells compared to mice with TNF-alpha-sufficient B cells. To confirm that the reduced atherosclerosis is attributable to B2 cells, we transferred wild-type and TNF-alpha-deficient B2 cells into ApoE(-/-) mice deficient in B cells or in lymphocytes. After 8 weeks of high fat diet, we found that atherosclerosis was increased by wild-type but not TNF-alpha-deficient B2 cells. Lesions of mice with wild-type B2 cells but not TNF-alpha-deficient B2 cells also had increased apoptotic cells and necrotic cores. Transferred B2 cells were found in lesions of recipient mice, suggesting that TNF-alpha-producing B2 cells promote atherosclerosis within lesions. CONCLUSION: We conclude that TNF-alpha produced by B2 cells is a key mechanism by which B2 cells promote atherogenesis through augmenting macrophage TNF-alpha production to induce cell death and inflammation that promote plaque vulnerability. |
