Effect of ApoE in communicating immunometabolic signaling in recipient macrophages via exosomes

While ApoE expression by myeloid cells is recognized to control inflammation, whether such benefits can be communicated via extracellular vesicles including exosomes is not known. Through the study of exosomes produced by macrophages derived from the bone marrow of Wildtype (WT-BMDM-exo) and ApoE deficient (EKO-BMDM-exo) mice, we uncover a critical role of ApoE in regulating cell signaling properties. We treated BMDM with EKO-BMDM-exo, WT-BMDM-exo, or PBS and performed gene expression profiling analysis. We found that BMDM treated with EKO-BMDM-exo show reductions in the cholesterol efflux gene Abca1 and the long chain fatty acid transporter Cpt1a. Furthermore, BMDM treated with EKO-BMDM-exo show reduced expressions of genes involved in oxidative stress response, particularly the glutathione peroxidases (Gpx1 & Gpx3) and the selenoproteins (Selenow, Selenom, Selenop, and Selenon). In contrast, treatments of these EKO-BMDM-exo upregulated the expressions of genes reported to drive glycolysis or involved in the glycolytic pathway (Aldh2, Pkm, Cd9, Fth1, Dio2, and Pgd). Taken together, our data unveil a novel property of macrophage ApoE in controlling the immunometabolism-regulatory properties by their secreted exosomes. To investigate the differential expression of mRNAs in BMDM treated with exosomes derived from the bone marrow of Wildtype (WT-BMDM-exo) and ApoE deficient (EKO-BMDM-exo) mice, or PBS as control. Bone marrow cells are taken from male mice that are 6- to 12-week-old and cultured into BMDM. Cells are then treated with EKO-BMDM-exo, or WT-BMDM-exo, or PBS for 18 hours. We then collected the total RNA and performed gene expression profiling analysis using data obtained from RNA-seq of the three different cell groups. Three biological replicates (n = 3) were used for each group.