Department for BioMedical Research DBMR, Department of Pulmonary Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Telethon Kids Institute, University of Western Australia, Nedlands, WA, Australia.
Clin Exp Med. 2023 Aug;23(4):1075-1088. doi: 10.1007/s10238-022-00945-7. Epub 2022 Nov 20.
Idiopathic pulmonary fibrosis (IPF) is characterized by permanent scarring of lung tissue and declining lung function, and is an incurable disease with increase in prevalence over the past decade. The current consensus is that aberrant wound healing following repeated injuries to the pulmonary epithelium is the most probable cause of IPF, with various immune inflammatory pathways having been reported to impact disease pathogenesis. While the role of immune cells, specifically T lymphocytes and regulatory T cells (Treg), in IPF pathogenesis has been reported and discussed recently, the pathogenic or beneficial roles of these cells in inducing or preventing lung fibrosis is still debated. This lack of understanding could be due in part to the difficulty in obtaining diseased human lung tissue for research purposes. For this reason, many animal models have been developed over the years to attempt to mimic the main clinical hallmarks of IPF: among these, inducing lung injury in rodents with the anti-cancer agent bleomycin has now become the most commonly studied animal model of IPF. Pulmonary fibrosis is the major side effect when bleomycin is administered for cancer treatment in human patients, and a similar effect can be observed after intra-tracheal administration of bleomycin to rodents. Despite many pathophysiological pathways of lung fibrosis having been investigated in bleomycin-injured animal models, one central facet still remains controversial, namely the involvement of specific T lymphocyte subsets, and in particular Treg, in disease pathogenesis. This review aims to summarize the major findings and conclusions regarding the involvement of immune cells and their receptors in the pathogenesis of IPF, and to elaborate on important parallels between animal models and the human disease. A more detailed understanding of the role of Treg and other immune cell subsets in lung injury and fibrosis derived from animal models is a critical basis for translating this knowledge to the development of new immune-based therapies for the treatment of human IPF.
特发性肺纤维化（IPF）的特征是肺组织永久性瘢痕形成和肺功能下降，是一种无法治愈的疾病，在过去十年中患病率有所增加。目前的共识是，肺上皮细胞反复受伤后的异常愈合是 IPF 最可能的原因，已经报道了各种免疫炎症途径影响疾病的发病机制。虽然免疫细胞，特别是 T 淋巴细胞和调节性 T 细胞（Treg）在 IPF 发病机制中的作用最近已经被报道和讨论，但这些细胞在诱导或预防肺纤维化中的致病或有益作用仍存在争议。这种理解上的不足可能部分归因于难以获得用于研究目的的患病人类肺组织。出于这个原因，多年来已经开发了许多动物模型来试图模拟 IPF 的主要临床特征：其中，用抗癌药物博莱霉素诱导啮齿动物的肺损伤现在已成为研究最广泛的 IPF 动物模型。博莱霉素在人类癌症患者中的治疗中会引起肺纤维化，而在博莱霉素经气管内给药后，在啮齿动物中也可以观察到类似的效果。尽管在博莱霉素损伤的动物模型中已经研究了许多肺纤维化的病理生理途径，但一个核心方面仍然存在争议，即特定 T 淋巴细胞亚群，特别是 Treg，在疾病发病机制中的参与。这篇综述旨在总结关于免疫细胞及其受体在 IPF 发病机制中的参与的主要发现和结论，并详细阐述动物模型和人类疾病之间的重要相似之处。更详细地了解 Treg 和其他免疫细胞亚群在动物模型中的肺损伤和纤维化中的作用是将这方面知识转化为治疗人类 IPF 的新免疫治疗方法的关键基础。
