"Briefly, HEK293T cells were seeded at 70,000 cells per cm2 in 15 cm tissue culture dishes in 20 mL media (DMEM, 10% FBS) and incubated overnight at 37°C, 5% CO2. Twenty-four hours after plating, 12 μg of lentiviral transfer vector was transfected alongside 7 μg psPAX2 (Addgene), and 3 μg pMD2.G (Addgene) with 50 μL jetPRIME transfection reagent (Polyplus) according to manufacturer’s protocol. "

Developing strategies that promote the resolution of vascular inflammation and atherosclerosis remains a major therapeutic challenge. Here, we show that exosomes produced by naive bone marrow-derived macrophages (BMDM-exo) contain anti-inflammatory microRNA-99a/146b/378a that are further increased in exosomes produced by BMDM polarized with IL-4 (BMDM-IL-4-exo). These exosomal microRNAs suppress inflammation by targeting NF-κB and TNF-α signaling and foster M2 polarization in recipient macrophages. Repeated infusions of BMDM-IL-4-exo into Apoe^-/- mice fed a Western diet reduce excessive hematopoiesis in the bone marrow and thereby the number of myeloid cells in the circulation and macrophages in aortic root lesions. This also leads to a reduction in necrotic lesion areas that collectively stabilize atheroma. Thus, BMDM-IL-4-exo may represent a useful therapeutic approach for atherosclerosis and other inflammatory disorders by targeting NF-κB and TNF-α via microRNA cargo delivery.