Exosomes-mediated phenotypic switch of macrophages in the immune microenvironment after spinal cord injury

• Published in: Biomedicine & pharmacotherapy Vol. 144; p. 112311
• Main Authors: Peng, Peng, Yu, Hao, Xing, Cong, Tao, Bo, Li, Chao, Huang, Jingyuan, Ning, Guangzhi, Zhang, Bin, Feng, Shiqing
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01.12.2021; Elsevier
• Subjects: Animals; Cell Plasticity; Cellular Microenvironment - immunology; Disease Models, Animal; Exosomes; Exosomes - immunology; Exosomes - metabolism; Exosomes - transplantation; Immune microenvironment; Macrophage polarization; Macrophages - immunology; Macrophages - metabolism; Macrophages - transplantation; Male; Mice; Mice, Inbred C57BL; MicroRNAs - genetics; MicroRNAs - metabolism; MiRNA-mRNA network; Phenotype; Phosphatidylinositol 3-Kinase - metabolism; Proto-Oncogene Proteins c-akt - metabolism; PTEN Phosphohydrolase - genetics; PTEN Phosphohydrolase - metabolism; Rats; Rats, Wistar; RAW 264.7 Cells; Signal Transduction; Spinal Cord - immunology; Spinal Cord - metabolism; Spinal Cord Injuries - genetics; Spinal Cord Injuries - immunology; Spinal Cord Injuries - metabolism; Spinal Cord Injuries - surgery; Spinal cord injury; Immune microenvironment; DE; IL; Arg1; Macrophage polarization; CIBERSORT; PTEN; CNS; BMDM; Spinal cord injury; Exosomes; LPS; MiRNA-mRNA network; IFN-γ; PI3K; TNF-α; Notch1; Exos; SCI; miRNA; Top1; Pou4f2
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2021.112311

Although accumulating evidence indicated that modulating macrophage polarization could ameliorate the immune microenvironment and facilitate the repair of spinal cord injury (SCI), the underlying mechanism of macrophage phenotypic switch is still poorly understood. Exosomes (Exos), a potential tool of cell-to-cell communication, may play important roles in cell reprogramming. Herein, we investigated the roles of macrophages-derived exosomes played for macrophage polarization in the SCI immune microenvironment. In this study, we found the fraction of M2 macrophages was markedly decreased after SCI. Moreover, the M2 macrophages-derived exosomes could increase the percentage of M2 macrophages, decrease that of M1 macrophages while the M1 macrophages-derived exosomes acted oppositely. According to the results of in silico analyses and molecular experiments verification, this phenotypic switch might be mediated by the exosomal miRNA-mRNA network, in which the miR-23a-3p/PTEN/PI3K/AKT axis might play an important role. In conclusion, our study suggests macrophage polarization that regulated by various interventions might be mediated by their own exosomes at last. Moreover, M2 macrophages-derived exosomes could promote M2 macrophage polarization via the potential miRNA-mRNA network. Considering its potential of modulating polarization, M2 macrophages-derived exosomes may be a promising therapeutic agent for SCI repair. [Display omitted] •Macrophage polarization that regulated by various interventions might be mediated by their own exosomes.•The underlying mechanism might be the exosomal miRNA-mRNA interaction network.•The miR-23a-3p/PTEN/PI3K/AKT axis was notable in the network.•M2 macrophages-derived exosomes may be a promising therapeutic agent for SCI repair.