Advances in understanding exosome-mediated regulation of macrophage function.

Exosomes serve as crucial mediators of intercellular communication, regulating cellular functions by carrying proteins, nucleic acids, and lipids. As core components of the immune system, macrophages are closely associated with exosomes. This review focuses on three main aspects: functional outcomes, signaling pathways, and regulatory mechanisms. In terms of functional outcomes, exosomes from different origins influence macrophage polarization, activation, recruitment, and programmed cell death. Regarding signaling pathways, exosomes function primarily through two distinct modules-the conserved core pathways, represented by PI3K/Akt, STAT3, and NF-κB, and the context-dependent mechanisms, represented by MAPK and PTEN. With respect to regulatory modes, exosomes control macrophage functional differentiation via non-coding RNAs and metabolic reprogramming. In addition, this review compares the heterogeneity of exosomes derived from different sources, analyzes the mechanisms and selectivity of exosome uptake by macrophages, and outlines the key challenges and strategies for clinical translation. In summary, exosomes regulate macrophage function through multiple pathways and targets, playing critical roles in tumor biology, inflammation, and tissue repair. A deeper understanding of these mechanisms may provide new insights and therapeutic targets for exosome-based applications.