The guardians of pulmonary harmony: alveolar macrophages orchestrating the symphony of lung inflammation and tissue homeostasis

IF 9 1区 医学 Q1 RESPIRATORY SYSTEM
Learta Pervizaj-Oruqaj, Maximiliano Ruben Ferrero, Ulrich Matt, Susanne Herold
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Abstract

Recent breakthroughs in single-cell sequencing, advancements in cellular and tissue imaging techniques, innovations in cell lineage tracing, and insights into the epigenome collectively illuminate the enigmatic landscape of alveolar macrophages in the lung under homeostasis and disease conditions. Our current knowledge reveals the cellular and functional diversity of alveolar macrophages within the respiratory system, emphasising their remarkable adaptability. By synthesising insights from classical cell and developmental biology studies, we provide a comprehensive perspective on alveolar macrophage functional plasticity. This includes an examination of their ontology-related features, their role in maintaining tissue homeostasis under steady-state conditions and the distinct contribution of bone marrow-derived macrophages (BMDMs) in promoting tissue regeneration and restoring respiratory system homeostasis in response to injuries. Elucidating the signalling pathways within inflammatory conditions, the impact of various triggers on tissue-resident alveolar macrophages (TR-AMs), as well as the recruitment and polarisation of macrophages originating from the bone marrow, presents an opportunity to propose innovative therapeutic approaches aimed at modulating the equilibrium between phenotypes to induce programmes associated with a pro-regenerative or homeostasis phenotype of BMDMs or TR-AMs. This, in turn, can lead to the amelioration of disease outcomes and the attenuation of detrimental inflammation. This review comprehensively addresses the pivotal role of macrophages in the orchestration of inflammation and resolution phases after lung injury, as well as ageing-related shifts and the influence of clonal haematopoiesis of indeterminate potential mutations on alveolar macrophages, exploring altered signalling pathways and transcriptional profiles, with implications for respiratory homeostasis.

肺部和谐的守护者:肺泡巨噬细胞协调肺部炎症和组织平衡的交响乐
单细胞测序技术的最新突破、细胞和组织成像技术的进步、细胞系追踪技术的创新以及对表观基因组的深入研究共同揭示了肺泡巨噬细胞在平衡和疾病条件下的神秘面纱。我们目前的知识揭示了肺泡巨噬细胞在呼吸系统中的细胞和功能多样性,强调了它们非凡的适应性。通过综合经典细胞和发育生物学研究的见解,我们提供了一个关于肺泡巨噬细胞功能可塑性的全面视角。这包括研究它们与本体相关的特征、它们在稳态条件下维持组织稳态的作用,以及骨髓源性巨噬细胞(BMDMs)在促进组织再生和恢复呼吸系统稳态以应对损伤方面的独特贡献。阐明炎症条件下的信号通路、各种诱因对组织驻留肺泡巨噬细胞(TR-AMs)的影响以及源自骨髓的巨噬细胞的招募和极化,为提出创新性治疗方法提供了机会,这些方法旨在调节表型之间的平衡,以诱导与 BMDMs 或 TR-AMs 的促进再生或平衡表型相关的程序。这反过来又能改善疾病的预后并减轻有害炎症。这篇综述全面论述了巨噬细胞在协调肺损伤后的炎症和缓解阶段中的关键作用,以及与衰老相关的转变和肺泡巨噬细胞不确定潜能突变的克隆造血的影响,探讨了信号通路和转录谱的改变,以及对呼吸稳态的影响。
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来源期刊
European Respiratory Review
European Respiratory Review Medicine-Pulmonary and Respiratory Medicine
CiteScore
14.40
自引率
1.30%
发文量
91
审稿时长
24 weeks
期刊介绍: The European Respiratory Review (ERR) is an open-access journal published by the European Respiratory Society (ERS), serving as a vital resource for respiratory professionals by delivering updates on medicine, science, and surgery in the field. ERR features state-of-the-art review articles, editorials, correspondence, and summaries of recent research findings and studies covering a wide range of topics including COPD, asthma, pulmonary hypertension, interstitial lung disease, lung cancer, tuberculosis, and pulmonary infections. Articles are published continuously and compiled into quarterly issues within a single annual volume.
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