Kapellos Theodore S, Conlon Thomas M, Yildirim Ali Önder, Lehmann Mareike
Comprehensive Pneumology Center, Institute of Lung Health and Immunity, Helmholtz Munich, Member of the German Center for Lung Research (DZL), Munich, Germany.
Institute of Experimental Pneumology, University Hospital, Ludwig Maximilians University of Munich, Munich, Germany.
Eur Respir J. 2023 Oct 12;62(4). doi: 10.1183/13993003.00589-2023. Print 2023 Oct.
COPD is a devastating respiratory condition that manifests persistent inflammation, emphysema development and small airway remodelling. Lung regeneration is defined as the ability of the lung to repair itself after injury by the proliferation and differentiation of progenitor cell populations, and becomes impaired in the COPD lung as a consequence of cell intrinsic epithelial stem cell defects and signals from the micro-environment. Although the loss of structural integrity and lung regenerative capacity are critical for disease progression, our understanding of the cellular players and molecular pathways that hamper regeneration in COPD remains limited. Intriguingly, despite being a key driver of COPD pathogenesis, the role of the immune system in regulating lung regenerative mechanisms is understudied. In this review, we summarise recent evidence on the contribution of immune cells to lung injury and regeneration. We focus on four main axes: 1) the mechanisms which myeloid cells cause alveolar degradation; 2) the formation of tertiary lymphoid structures and the production of autoreactive antibodies; 3) the consequences of inefficient apoptotic cell removal; and 4) the effects of innate and adaptive immune cell signalling on alveolar epithelial proliferation and differentiation. We finally provide insight on how recent technological advances in omics technologies and human lung models can delineate immune cell-epithelium cross-talk and expedite precision pro-regenerative approaches toward reprogramming the alveolar immune niche to treat COPD.
慢性阻塞性肺疾病（COPD）是一种严重的呼吸系统疾病，表现为持续炎症、肺气肿发展和小气道重塑。肺再生是指肺在损伤后通过祖细胞群体的增殖和分化进行自我修复的能力，而在COPD患者的肺中，由于细胞内在的上皮干细胞缺陷和微环境信号，肺再生能力受损。尽管结构完整性的丧失和肺再生能力对疾病进展至关重要，但我们对阻碍COPD中再生的细胞成分和分子途径的了解仍然有限。有趣的是，尽管免疫系统是COPD发病机制的关键驱动因素，但其在调节肺再生机制中的作用却研究不足。在这篇综述中，我们总结了关于免疫细胞对肺损伤和再生作用的最新证据。我们重点关注四个主要方面：1）髓样细胞导致肺泡降解的机制；2）三级淋巴结构的形成和自身反应性抗体的产生；3）凋亡细胞清除效率低下的后果；4）固有免疫和适应性免疫细胞信号对肺泡上皮细胞增殖和分化的影响。我们最后深入探讨了组学技术和人类肺模型的最新技术进展如何描绘免疫细胞与上皮细胞的相互作用，并加快精准的促再生方法，以重新编程肺泡免疫微环境来治疗COPD。
