Subcutaneous injection of dendritic cells aggravates atherosclerosis in ApoE-knockout mice by activation of TLR4

Dendritic cells (DCs) are specialized antigen-presenting cells which are important in immune diseases, in particular atherosclerosis, a chronic inflammatory disease, however their role in atherosclerosis-associated immunity is unclear. To evaluate the role of DCs in atherosclerosis, exogenous bone marrow-derived DCs were transferred into ApoE(−/−) mice in the present study. The extent of disease was measured in the aorta and was compared with mice treated with phosphate-buffered saline (PBS) or left untreated and fed a western diet. Mice receiving exogenous DCs demonstrated significantly larger atherosclerotic lesions compared with the mice treated with PBS, with increasing numbers of mature DCs in circulation and enhanced DC infiltration into plaque lesions, in addition to activation of circulating inflammatory components and atherosclerotic lesions. Furthermore, it was demonstrated that exogenous DCs upregulated the expression of Toll-like receptor 4 (TLR4) on DCs, which may be an important mechanism to activate DCs and aggravate atherosclerosis. Therefore the present study concluded that exogenous DCs may induce maturation of endogenous DCs via upregulation of TLR4, further increasing the inflammatory response and accelerating atherosclerosis.