Vasarmidi Eirini, Worrell Julie C, Mahmutovic Persson Irma, Yaqub Naheem, Miądlikowska Ewa, Barnig Cindy, Boots Agnes, Reynaert Niki L, Cuevas Ocaña Sara
Department of Respiratory Medicine, Laboratory of Molecular and Cellular Pneumonology, School of Medicine, University of Crete, Heraklion, Greece.
These authors contributed equally.
Breathe (Sheff). 2025 May 13;21(2):240261. doi: 10.1183/20734735.0261-2024. eCollection 2025 Apr.
This review summarises some of the key features of interstitial lung diseases (ILDs) from a translational science point of view and brings insights into potential therapeutic options. Genetic predisposition and environmental factors like smoking, pollution and infections significantly impact the onset, progression and treatment response in ILDs, highlighting the need for personalised management. Fibroblasts are central to ILD pathology, influencing the tissue microenvironment, immune cell interactions and extracellular matrix (ECM) production, making them critical therapeutic targets. Monocyte-derived M2 macrophages drive fibrosis in idiopathic pulmonary fibrosis by secreting cytokines and remodelling the ECM. Understanding macrophage subtypes and their dynamics offers new therapeutic possibilities. Chronic type 2 immunity contributes to fibrosis, emphasising the need to enhance protective markers in order to even out the balance shift of pathological immune responses in ILD treatments. Serum biomarkers like Krebs von den Lungen-6 (KL-6), surfactant protein (SFTP) D, matrix metalloproteinase-7 (MMP-7), and C-C motif chemokine ligand (CCL)-18 are valuable for diagnosing and predicting ILD progression, although more research is needed for clinical application. Animal models, especially bleomycin-based models, offer insights into ILD pathology, but challenges like lung hyperinflation highlight the need for careful model selection and translational research to bridge preclinical and clinical findings.
本综述从转化科学的角度总结了间质性肺疾病(ILDs)的一些关键特征,并深入探讨了潜在的治疗选择。遗传易感性以及吸烟、污染和感染等环境因素对ILDs的发病、进展和治疗反应有显著影响,这凸显了个性化管理的必要性。成纤维细胞在ILD病理过程中起着核心作用,影响组织微环境、免疫细胞相互作用和细胞外基质(ECM)的产生,使其成为关键的治疗靶点。单核细胞衍生的M2巨噬细胞通过分泌细胞因子和重塑ECM来驱动特发性肺纤维化中的纤维化。了解巨噬细胞亚型及其动态变化提供了新的治疗可能性。慢性2型免疫促进纤维化,强调在ILD治疗中需要增强保护性标志物,以平衡病理性免疫反应的失衡。血清生物标志物如克雷布斯-冯-登-卢肯-6(KL-6)、表面活性蛋白(SFTP)D、基质金属蛋白酶-7(MMP-7)和C-C基序趋化因子配体(CCL)-18对诊断和预测ILD进展有价值,尽管临床应用还需要更多研究。动物模型,尤其是基于博来霉素的模型,有助于深入了解ILD病理,但肺过度充气等挑战凸显了仔细选择模型和进行转化研究以弥合临床前和临床研究结果的必要性。