M2-type macrophage nanovesicles regulate the inflammatory response after necrotizing enterocolitis by inducing M1 to M2-like macrophage polarization.

Abstract

Necrotizing enterocolitis (NEC) is a serious inflammatory gastrointestinal disorder leading to a devastating intestinal inflammatory response, which typically results in severe sepsis and death. Given the imbalance of inflammatory response in the intestine that results in immune dysregulation and further worsens the clinical symptoms of NEC. Macrophages are the primary cells responsible for the early regulation and resolution of intestinal inflammation, therefore our experiments focus on the regulation of the polarization type of macrophages. In this study, we applied a convenient and continuous extrusion system to execute and purify M2NVs from RAW264.7 macrophage cells, then used to interfere with the LPS-induced cell inflammation model and NEC animal model. We discovered that M2NVs could foster the polarization of M1 to M2 macrophages and inhibit inflammatory injury, aligning with theresults. Meanwhile, our study also revealed that M2NVs intervention could not only effectively alleviate the intestinal inflammatory environment, but also affect the changes in intestinal metabolism via omics techniques. Overall, the engineering strategy of M2NVs represents a promising approach with great potential for NEC treatment.