Neutrophil heterogeneity in Kawasaki disease and multisystem inflammatory syndrome in children

Neutrophils, specialized cells of the early innate immune response, are important for maintaining the body's internal homeostasis. Upon invasion by foreign microbes, neutrophils are swiftly activated and recruited to the infection site, where they perform bactericidal functions through phagocytic clearance, degranulation-mediated toxin release, and NADPH oxidase-dependent killing. While their presence is crucial in the early stages of inflammation to combat infection, the prolonged engagement of neutrophils at the infection site can cause tissue damage due to apoptosis and the release of cytotoxic mediators. Neutrophils exhibit significant heterogeneity in response to allostatic conditions, with their phenotypic and functional properties undergoing distinct changes. Therefore, understanding the heterogeneity and diversity of neutrophils under physiological and pathological conditions is important. Multisystem inflammatory syndrome in children (MIS-C) is a pediatric inflammatory syndrome that emerges following exposure to SARS-CoV-2, while Kawasaki disease (KD) is a childhood systemic vasculitis with unknown etiology. Both conditions share clinical features, including neutrophilia and cardiovascular complications. This suggests the likelihood of overlapping underlying immunopathogenic mechanisms, and neutrophils may play a crucial role in these processes. This review focuses on the heterogeneity and function of neutrophils in KD and MIS-C, providing a comprehensive overview of the current research in this field. IMPACT: Neutrophils exhibit significant heterogeneity under physiological and pathological states. Different neutrophil subsets perform diverse functional characteristics. KD and MIS-C have apparent phenotypic similarities of systemic inflammation and cardiovascular complications. Neutrophil heterogeneity correlates with disease severity, and studies of neutrophil subsets reveal potential shared immunological drivers. Multi-omics analysis of neutrophil heterogeneity helps to better understand neutrophil subsets and discover new functions. Research into MIS-C and KD enhances our understanding of pediatric inflammatory diseases with cardiovascular involvement.