Gamma irradiation-engineered macrophage-derived exosomes as potential immunomodulatory therapeutic agents.

ABSTRACT

The modulation of macrophage polarization is a promising strategy for maintaining homeostasis and improving innate and adaptive immunity. Low-dose ionizing radiation has been implicated in macrophage immunomodulatory responses. However, studies on the relationship between exosomes and regulation of macrophage polarization induced by ionizing radiation are limited. Therefore, this study investigated the alterations in macrophages and exosomes induced by gamma irradiation and elucidated the underlying mechanisms. We used the mouse macrophage cell line RAW 264.7 to generate macrophages and performed western blot, quantitative reverse transcription-PCR, and gene ontology analyses to elucidate the molecular profiles of macrophage-derived exosomes under varying treatment conditions, including 10 Gy gamma irradiation. Exosomes isolated from gamma-irradiated M1 macrophages exhibited an enhanced M1 phenotype. Irradiation induced the activation of NF-κB and NLRP3 signaling in M1 macrophages, thereby promoting the expression of pro-inflammatory cytokines. Cytokine expression was also upregulated in gamma-irradiated M1 macrophage-released exosomes. Therefore, gamma irradiation has a remarkable effect on the immunomodulatory mechanisms and cytokine profiles of gamma-irradiated M1 macrophage-derived exosomes, and represents a potential immunotherapeutic modality.