UCSF

Proper regulation of inflammatory responses is critical for effective microglia function in physiology and disease. While much emphasis is placed on mechanisms driving microglia activation, there remains a gap in knowledge on how microglia resolve or modulate inflammatory activation. Here we provide a comprehensive analysis of exosome regulation of microglia inflammatory response, highlighting a novel anti-inflammatory function of exosomes. First, microglia-derived exosomes contain immune molecules that are sufficient to propagate signals driving transcriptional changes associated with increased inflammatory cytokine production and phagocytic clearance in recipient microglia. Secondly, microglia with impaired exosome biogenesis display altered inflammatory kinetics, characterized by exaggerated and prolonged expression of pro-inflammatory molecules in response to acute and chronic aging-associated inflammation. This robust anti-inflammatory function of exosomes is manifested in part through the release of proinflammatory microRNAs, such miR-155. Taken together, our study identifies exosomes as critical mediators of inflammatory communication in the brain that play important roles in intracellular resolution of microglia inflammation.