Effect of ApoE in communicating CD4+ T cell activation and proliferation
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 splenic CD4+ T cells with EKO-BMDM-exo, WT-BMDM-exo, or PBS and performed gene expression profiling analysis. We found that CD4+ T cells treated with EKO-BMDM-exo show elevations in genes involved in the T-cell receptor complex (Cd3e, Cd247, & Cd4) and Il2rg, a key component of cytokine receptors on CD4+ T cells. Taken together, our data unveil a novel property of macrophage ApoE in controlling adaptive immunity by their secreted exosomes. Overall design: To investigate the differential expression of mRNAs in splenic CD4+ T cells treated with exosomes derived from the bone marrow of Wildtype (WT-BMDM-exo) and ApoE deficient (EKO-BMDM-exo) mice, or PBS as control. Splenic CD4+ T cells are taken from male mice that are 6- to 12-week-old and stimulated with anti-CD3/anti-CD28 beads and murine IL-2. 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.