IL-33 promotes cardiovascular lesions development in a mouse model of Kawasaki Disease

Abstract Kawasaki Disease (KD), a pediatric acute febrile illness and systemic vasculitis, is the leading cause of acquired heart diseases in children. Coronary artery aneurysms (CAAs) occur up to 25% untreated children, which reduced 5% with intravenous immunoglobulin (IVIG) treatment. However, 20% KD patients are refractory IVIG at higher risk CAAs, highlighting need characterize mechanisms mediating vasculitis develop more efficient therapies. IL-33 released upon inflammation tissue damage exerts its effects by binding receptor ST2 (IL1RL1). Levels elevated during phase. how contributes development cardiovascular lesions remains unknown. Using Lactobacillus casei cell wall extract (LCWE) murine model we observed increased Il33 mRNA expression hearts abdominal aortas LCWE-injected mice. While was detected immunofluorescence both control mice, mainly tissues from Single-cell RNA-sequencing mice indicated that transcripts were expressed primarily fibroblasts, endothelial cells, B vascular smooth muscle cells. In contrast, Il1rl1 highly infiltrating regulatory T macrophages, eosinophils, neutrophils. Blocking either anti-IL-33 antibody or using −/−mice significantly attenuated LCWE-induced vasculitis. Our results indicate promotes could therapeutically be targeted inhibit lesions.