Institute of Cardiovascular Physiology and Pathophysiology, Walter Brendel Center for Experimental Medicine Biomedical Center (BMC), Ludwig-Maximilians-Universität München, Munich, Germany.
Institute of Immunology, Universität of Münster, Münster, Germany.
Nephrol Dial Transplant. 2024 Sep 27;39(10):1551-1564. doi: 10.1093/ndt/gfad266.
Neutrophils, the most abundant white blood cells in the human circulation, play crucial roles in various diseases, including kidney disease. Traditionally viewed as short-lived pro-inflammatory phagocytes that release reactive oxygen species, cytokines and neutrophil extracellular traps, recent studies have revealed their complexity and heterogeneity, thereby challenging this perception. Neutrophils are now recognized as transcriptionally active cells capable of proliferation and reverse migration, displaying phenotypic and functional heterogeneity. They respond to a wide range of signals and deploy various cargo to influence the activity of other cells in the circulation and in tissues. They can regulate the behavior of multiple immune cell types, exhibit innate immune memory, and contribute to both acute and chronic inflammatory responses while also promoting inflammation resolution in a context-dependent manner. Here, we explore the origin and heterogeneity of neutrophils, their functional diversity, and the cues that regulate their effector functions. We also examine their emerging role in infectious and non-infectious diseases with a particular emphasis on kidney disease. Understanding the complex behavior of neutrophils during tissue injury and inflammation may provide novel insights, thereby paving the way for potential therapeutic strategies to manage acute and chronic conditions. By deciphering their multifaceted role, targeted interventions can be developed to address the intricacies of neutrophil-mediated immune responses and improve disease outcomes.
中性粒细胞是人类循环中最丰富的白细胞,在各种疾病中发挥着关键作用,包括肾脏疾病。传统上,中性粒细胞被视为寿命短的促炎吞噬细胞,会释放活性氧物质、细胞因子和中性粒细胞胞外诱捕网,但最近的研究揭示了它们的复杂性和异质性,从而挑战了这一观点。中性粒细胞现在被认为是具有转录活性的细胞,能够增殖和反向迁移,表现出表型和功能的异质性。它们对广泛的信号作出反应,并释放各种货物,以影响循环中和组织中的其他细胞的活性。它们可以调节多种免疫细胞类型的行为,表现出先天免疫记忆,并在急性和慢性炎症反应中发挥作用,同时以依赖于上下文的方式促进炎症的解决。在这里,我们探讨了中性粒细胞的起源和异质性、它们的功能多样性以及调节其效应功能的线索。我们还研究了它们在感染和非感染性疾病中的新兴作用,特别强调了肾脏疾病。了解中性粒细胞在组织损伤和炎症过程中的复杂行为可能提供新的见解,从而为管理急性和慢性疾病的潜在治疗策略铺平道路。通过破译它们的多方面作用,可以开发靶向干预措施来解决中性粒细胞介导的免疫反应的复杂性,并改善疾病结局。