Interleukin-33/ST2 axis in Kawasaki disease: biology, vascular pathology, and future therapeutic strategies

INTRODUCTION: Kawasaki disease (KD) is an acute systemic vasculitis of childhood and the leading cause of acquired heart disease in developed countries. Coronary artery abnormalities (CAAs), the major clinical sequelae of KD, remain major clinical challenges, which highlights the need for deeper mechanistic insights. AREAS COVERED: This review summarizes current knowledge of the interleukin-33 (IL-33)/suppression of tumorigenicity 2 (ST2) axis in the context of KD. We discuss the molecular biology of IL-33 and its receptors, downstream signaling pathways, and cell-type-specific immunological and vascular effects. Evidence from clinical studies, biomarker analyses, and experimental KD models is integrated to delineate the potential contribution of IL-33/ST2 signaling to coronary arteritis. Relevant literature was identified through comprehensive searches of major biomedical databases focusing on KD, vasculitis, IL-33, ST2, and related therapeutic strategies. Literature was identified via PubMed and ClinicalTrials.gov. EXPERT OPINION: Current evidence supports the IL-33/ST2 axis as a plausible, context-dependent modulatory pathway linking tissue injury, innate immune activation, and vascular inflammation in KD. Soluble ST2 shows particular promise as a biomarker reflecting disease activity and cardiac stress. Targeted modulation of IL-33/ST2 signaling, guided by disease phase and biomarker profiles, could represent a next-generation therapeutic approach to prevent CAAs in KD.