The Dual Role of Exosomes in Gout: From Inflammatory Amplifiers to Therapeutic Regulators

Gout is a metabolic disorder where excessive MSU crystals are found in joints and adjacent tissues. When the crystals are deposited acutely, they typically trigger loud and uncontrollable local inflammation. As we know, the main goals of diagnosis and treatment of the disease are the reduction of serum uric acid levels and treatment of acute inflammation. Although these methods are useful, we are still facing many challenges: early risk detection, personalized treatment plan and management of comorbidities associated with gout. As nanoscale vesicles for intercellular communication, exosomes are also receiving much attention due to their possible roles in the regulation of inflammation, pathogenesis and progression. We review the functions of exosomes in gout. Various mechanisms are known that exosomes regulate gouty inflammation. When immune cells activate MSU crystals, they release exosomes carrying mature IL-1β, NLRP3 inflammatory components and pro-inflammatory miRNAs that induce local inflammation. Exosomes from mesenchymal cells or other cell types may have other functions, such as NLRP3 inhibition and M2-polarized macrophage transporting the inflammation and tissue repair. It was carried out on vesicles collected from blood, synovial fluid, urine of patients for clinical studies. These vesicles differ in size, protein and miRNA expression because of the different stages of gout and could be the disease indicator. Most studies are still preliminary, small sample size and non-standard detection and evaluation. To translate these results into practice, more extensive prospective clinical trials are needed. Native and engineered exosomes are promising anti-inflammatory agents, modulating the immune system and facilitating precise tissue repair. Exosomes likely link MSU crystal deposition, acute inflammation and systemic immune metabolic dysregulation. Identifying the specific cell locations involved in gout is important for developing diagnostic and therapeutic approach for gout at earlier stages.