| First Author | Ng HP | Year | 2015 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 35 |
| Issue | 5 | Pages | 1101-12 |
| PubMed ID | 25792447 | Mgi Jnum | J:241629 |
| Mgi Id | MGI:5903198 | Doi | 10.1161/ATVBAHA.115.305290 |
| Citation | Ng HP, et al. (2015) Reduced Atherosclerosis in apoE-inhibitory FcgammaRIIb-Deficient Mice Is Associated With Increased Anti-Inflammatory Responses by T Cells and Macrophages. Arterioscler Thromb Vasc Biol 35(5):1101-12 |
| abstractText | OBJECTIVE: Fcgamma receptors (FcgammaRs) are classified as activating (FcgammaRI, III, and IV) and inhibitory (FcgammaRII) receptors. We have reported that deletion of activating FcgammaRs in apolipoprotein E (apoE) single knockout mice attenuated atherosclerosis. In this report, we investigated the hypothesis that deficiency of inhibitory FcgammaRIIb exacerbates atherosclerosis. APPROACH AND RESULTS: ApoE-FcgammaRIIb double knockout mice, congenic to the C57BL/6 (apoE-FcgammaRIIbB6 (-/-)), were generated and atherosclerotic lesions were assessed. In contrary to our hypothesis, when compared with apoE single knockout mice, arterial lesions were significantly decreased in apoE-FcgammaRIIbB6 (-/-) male and female mice fed chow or high-fat diets. Chimeric mice generated by transplanting apoE-FcgammaRIIbB6 (-/-) marrow into apoE single knockout mice also developed reduced lesions. CD4(+) T cells from apoE-FcgammaRIIbB6 (-/-) mice produced higher levels of interleukin-10 and transforming growth factor-beta than their apoE single knockout counterparts. As our findings conflict with a previous report using apoE-FcgammaRIIb129/B6 (-/-) mice on a mixed genetic background, we investigated whether strain differences contributed to the anti-inflammatory response. Macrophages from FcgammaRIIb129/B6 (-/-) mice on a mixed genetic background produced more interleukin-1beta and MCP-1 (monocyte chemoattractant protein-1) in response to immune complexes, whereas congenic FcgammaRIIbB6 (-/-) mice generated more interleukin-10 and significantly less interleukin-1beta. Interestingly, the expression of lupus-associated slam genes, located in proximity to fcgr2b in mouse chromosome 1, is upregulated only in mixed FcgammaRIIb129/B6 (-/-) mice. CONCLUSIONS: Our findings demonstrate a detrimental role for FcgammaRIIb signaling in atherosclerosis and the contribution of anti-inflammatory cytokine responses in the attenuated lesions observed in apoE-FcgammaRIIbB6 (-/-) mice. As 129/sv genome-derived lupus-associated genes have been implicated in lupus phenotype in FcgammaRIIb129/B6 (-/-) mice, our findings suggest possible epistatic mechanism contributing to the decreased lesions. |
