The Autophagy–Inflammation Axis in Kawasaki Disease: Pathogenic Mechanisms and Translational Opportunities

Kawasaki disease (KD) represents the foremost cause of acquired pediatric heart disease, with coronary artery injury being the principal factor contributing to adverse prognoses. A significant clinical challenge is that 20–30% of patients demonstrate resistance to intravenous immunoglobulin (IVIG), which markedly elevates the risk of coronary artery lesions and long-term cardiovascular sequelae. Consequently, there is an urgent need to investigate novel pathogenic mechanisms beyond the conventional cytokine storm theory and to identify effective therapeutic targets. This review systematically summarizes the key role of the autophagy–inflammation axis in KD vasculopathy. Current evidence indicates that defective mitophagy and lysosomal dysfunction induce mitochondrial DNA release, resulting in overactivation of the NLRP3 inflammasome and cGAS-STING pathways, which amplify inflammatory responses and aggravate endothelial damage. The regulation of this axis is dynamic during both the acute and recovery phases and is influenced by metabolic reprogramming and epigenetic modifications, which may partially explain the lack of response to IVIG. Pharmacological agents, such as rapamycin and metformin, as well as natural compounds, such as resveratrol and urolithin A, have demonstrated beneficial anti-inflammatory effects in preclinical studies. Targeting the autophagy–inflammation axis represents a significant research direction with the potential to evolve into a promising therapeutic strategy. Mechanistically, restoring the balance of the autophagy–inflammation axis holds promise for mitigating coronary complications and improving long-term cardiovascular outcomes in children with KD; however, this prospect requires validation through prospective clinical studies.