Wang Nana, Sun Ling, Qian Guanghui, Lv Haitao, Liu Zhiheng
Department of Cardiology, Children's Hospital of Soochow University, Suzhou, Jiangsu Province, China.
Institute of Pediatric Research, Children's Hospital of Soochow University, Suzhou, China.
Pediatr Res. 2025 Jun 19. doi: 10.1038/s41390-025-04200-z.
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.
中性粒细胞是早期固有免疫反应的特化细胞，对维持机体内部稳态至关重要。受到外来微生物侵袭时，中性粒细胞会迅速被激活并募集到感染部位，在那里它们通过吞噬清除、脱颗粒介导的毒素释放和依赖烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶的杀伤作用来发挥杀菌功能。虽然它们的存在在炎症早期对抗感染中至关重要，但中性粒细胞在感染部位的长期作用会因细胞凋亡和细胞毒性介质的释放而导致组织损伤。中性粒细胞在应对应激状态时表现出显著的异质性，其表型和功能特性会发生明显变化。因此，了解生理和病理条件下中性粒细胞的异质性和多样性很重要。儿童多系统炎症综合征（MIS-C）是一种在接触严重急性呼吸综合征冠状病毒2（SARS-CoV-2）后出现的儿科炎症综合征，而川崎病（KD）是一种病因不明的儿童系统性血管炎。这两种病症具有共同的临床特征，包括中性粒细胞增多和心血管并发症。这表明潜在的免疫致病机制可能存在重叠，并且中性粒细胞可能在这些过程中起关键作用。本综述聚焦于KD和MIS-C中中性粒细胞的异质性和功能，全面概述该领域的当前研究。影响：中性粒细胞在生理和病理状态下表现出显著的异质性。不同的中性粒细胞亚群具有不同的功能特性。KD和MIS-C在全身炎症和心血管并发症方面具有明显的表型相似性。中性粒细胞异质性与疾病严重程度相关，对中性粒细胞亚群的研究揭示了潜在的共同免疫驱动因素。对中性粒细胞异质性的多组学分析有助于更好地了解中性粒细胞亚群并发现新功能。对MIS-C和KD的研究增进了我们对伴有心血管受累的儿科炎症性疾病的理解。
