He Weifeng, Yan Lingfeng, Hu Dongxue, Hao Jianlei, Liou Yih-Cherng, Luo Gaoxing
Institute of Burn Research State Key Laboratory of Trauma and Chemical Poisoning the First Affiliated Hospital of Army Medical University (the Third Military Medical University) Chongqing China.
Chongqing Key Laboratory for Wound Repair and Tissue Regeneration Chongqing China.
MedComm (2020). 2025 Jan 21;6(2):e70063. doi: 10.1002/mco2.70063. eCollection 2025 Feb.
Neutrophils, the most abundant circulating leukocytes, have long been recognized as key players in innate immunity and inflammation. However, recent discoveries unveil their remarkable heterogeneity and plasticity, challenging the traditional view of neutrophils as a homogeneous population with a limited functional repertoire. Advances in single-cell technologies and functional assays have revealed distinct neutrophil subsets with diverse phenotypes and functions and their ability to adapt to microenvironmental cues. This review provides a comprehensive overview of the multidimensional landscape of neutrophil heterogeneity, discussing the various axes along which diversity manifests, including maturation state, density, surface marker expression, and functional polarization. We highlight the molecular mechanisms underpinning neutrophil plasticity, focusing on the complex interplay of signaling pathways, transcriptional regulators, and epigenetic modifications that shape neutrophil responses. Furthermore, we explore the implications of neutrophil heterogeneity and plasticity in physiological processes and pathological conditions, including host defense, inflammation, tissue repair, and cancer. By integrating insights from cutting-edge research, this review aims to provide a framework for understanding the multifaceted roles of neutrophils and their potential as therapeutic targets in a wide range of diseases.
中性粒细胞是循环中数量最多的白细胞，长期以来一直被认为是固有免疫和炎症的关键参与者。然而，最近的发现揭示了它们显著的异质性和可塑性，挑战了传统观念中认为中性粒细胞是具有有限功能的同质化群体的观点。单细胞技术和功能检测的进展揭示了具有不同表型和功能的独特中性粒细胞亚群，以及它们适应微环境线索的能力。本综述全面概述了中性粒细胞异质性的多维度格局，讨论了多样性表现的各种轴，包括成熟状态、密度、表面标志物表达和功能极化。我们强调了支撑中性粒细胞可塑性的分子机制，重点关注塑造中性粒细胞反应的信号通路、转录调节因子和表观遗传修饰之间的复杂相互作用。此外，我们探讨了中性粒细胞异质性和可塑性在生理过程和病理状况中的意义，包括宿主防御、炎症、组织修复和癌症。通过整合前沿研究的见解，本综述旨在提供一个框架，以理解中性粒细胞的多方面作用及其作为多种疾病治疗靶点的潜力。
