EXR-KJENS1DIAB-ST (Project)

Description:Macrophage-derived exosomes contribute to the pool of exosomes found in the circulation and atherosclerotic lesions. But whether they impact lesion dynamics is currently unknown. We showed that exosomes produced by bone marrow derived macrophage exposed to IL-4 (BMDM-IL-4-exo) displayed anti-inflammatory properties when tested in vitro. When infused into Apoe–/– mice, BMDM-IL4-exo polarized peritoneal macrophages into an M2 phenotype and reduced the number of myeloid cells in the circulation by controlling excessive hematopoiesis in the bone marrow. Although this did not reduced the lipid content of atherosclerotic lesions in the aortic root, it improved their inflammatory index by reducing the necrotic core and the number of lesional macrophages. Unbiased sequence analysis of BMDM-IL4-exo revealed an enrichment of microRNA-99a/146b/378a that all control macrophage inflammation. The selective loss of each of these microRNA in macrophage exosomes reduced their ability to control TNFa and NF-kB signaling. Together, our findings reveal a new anti-inflammatory property of M2-like macrophages via their regulated release of select microRNA in exosomes.

Creation Time:2020-02-10T00:00:00

Abbreviation:KJENS1DIAB