Abstract
Dendritic cells (DCs) play important roles in the initiation and maintenance of the immune response. The dysfunction of DCs contributes to tumor evasion and growth. Here we report our findings on the dysfunction of DCs in radiation-induced thymic lymphomas, and the up-regulation of the expression of the lipoprotein lipase (LPL) and the fatty acid binding protein (FABP4), and the level of triacylglycerol (TAG) in serum after total body irradiation, which contribute to DCs lipid accumulation. DCs with high lipid content showed low expression of co-stimulatory molecules and DCs-related cytokines, and were not able to effectively stimulate allogeneic T cells. Normalization of lipid abundance in DCs with an inhibitor of acetyl-CoA carboxylase restored the function of DCs. A high-fat diet promoted radiation-induced thymic lymphoma growth. In all, our study shows that dysfunction of DCs in radiation-induced thymic lymphomas was due to lipid accumulation and may represent a new mechanism in radiation-induced carcinogenesis.
Highlights
Dendritic cells (DCs) play important roles in the initiation and maintenance of the immune response
We report our findings on the dysfunction of DCs in radiation-induced thymic lymphomas, and the up-regulation of the expression of the lipoprotein lipase (LPL) and the fatty acid binding protein (FABP4), and the level of triacylglycerol (TAG) in serum after total body irradiation, which contribute to DCs lipid accumulation
We have previously shown that the activated ERK1/2 pathway may play a role, without involving STAT3, in the pathogenesis of c-ray-induced thymic lymphomas in BALB/c mice[4], and that TLR4-Knockout mice were protected from radiation-induced thymic lymphomas by down-regulation of IL-6 and miR-215
Summary
Dendritic cells (DCs) play important roles in the initiation and maintenance of the immune response. The adverse effect of dietary lipids intake on DCs functions has been confirmed by many studies[16,17,18,19,20] These findings prompted us to investigate the potential role of lipid accumulation and DCs function in radiation-induced thymic lymphomas. In this study we hypothesize that dysfunction of lipid metabolism leads to lipid accumulation in DCs, which in turn impairs the function of DCs and promotes thymic lymphomas growth. Our results support this hypothesis and may provide a new mechanism of radiation-induced carcinogenesis cancer via lipid accumulation
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