Enhanced lymphocyte infiltration in the liver of LDL receptor and Myeloid Differentiation 1 double knockout mice on high fat diet

Abstract

Abstract Myeloid differentiation 1 (MD-1; gene name: ly86 ), a glycoprotein that forms a complex with radioprotective protein 105 (RP105), is involved in the regulation of inflammation, obesity, and insulin resistance. Previous reports have shown an exacerbation of cardiac pathology in MD-1 deficient mice, including pressure overload-induced cardiac remodeling and high fat diet (HFD) -induced inflammatory atrial fibrosis. Furthermore, MD-1 expression is upregulated in atherosclerosis, as indicated by DEG database analysis, and is present in human atherosclerotic plaques. However, its involvement in atherosclerosis is unclear. In this study, we analyzed the effect of MD-1 deficiency on the development of HFD-induced atherosclerosis in littermates of low-density lipoprotein (LDL) receptor-deficient mice (LDLr −/− /MD-1 +/− and LDLr −/− /MD-1 −/− ). In contrast to RP105 deficient mice in previous reports, MD-1 deficiency did not clearly influence atherosclerosis development. However, LDLr −/− /MD-1 −/− mice exhibited significantly higher serum levels of total protein, triglycerides, cholesterol, LC/MS-detected lipophilic compounds, and an increased peripheral B-cell percentage with a Th2 antibody shift after 24 weeks of HFD. Furthermore, lymphocyte infiltration, predominantly of B2B cells and CD4 + T cells, was visible in random cross-sectional liver sections from LDLr −/− /MD-1 −/− mice. Our results indicated that MD-1 deficiency leads to further hyperlipidemia, Th2 shift, and enhances lymphocyte infiltration in the LDLr −/− liver.