Spatial profiling of Kawasaki disease cardiac inflammation identifies STING as a therapeutic target

The cellular subsets and in situ mechanisms underlying the development of coronary arteritis in Kawasaki disease (KD), the leading cause of acquired heart disease in children, remain poorly defined. We characterized the cellular composition and spatial organization of cardiac inflammation in autopsy coronary artery (CA) specimens from KD patients using 64-plex immunofluorescence. We identified spatially organized immune infiltrates of neutrophils, macrophages, and T cells associated with arterial wall destruction and remodeling, as well as disrupted stromal/muscle cell colocalization and diffuse myocardial inflammation. Spatial analysis also revealed expression of the innate immune sensor STING in myeloid cells in KD CA tissues. Pharmacological and genetic inhibition of STING reduced vasculitis development in a mouse model of KD. These findings define the spatial immune architecture of KD cardiac inflammation, reveal inflammatory injury beyond the coronary arteries, and identify STING as a potential therapeutic target for treatment-resistant or severe KD.