Braithwaite Adam T, Marriott Helen M, Lawrie Allan
Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Medical School, Sheffield, United Kingdom.
Front Med (Lausanne). 2018 Jul 27;5:212. doi: 10.3389/fmed.2018.00212. eCollection 2018.
The tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is a widely expressed cytokine that can bind five different receptors. TRAIL has been of particular interest for its proposed ability to selectively induce apoptosis in tumour cells. However, it has also been found to regulate a wide variety of non-canonical cellular effects including survival, migration and proliferation via kinase signalling pathways. Lung diseases represent a wide range of conditions affecting multiple tissues. TRAIL has been implicated in several biological processes underlying lung diseases, including angiogenesis, inflammation, and immune regulation. For example, TRAIL is detrimental in pulmonary arterial hypertension-it is upregulated in patient serum and lungs, and drives the underlying proliferative pulmonary vascular remodelling in rodent models. However, TRAIL protects against pulmonary fibrosis in mice models-by inducing apoptosis of neutrophils-and reduced serum TRAIL is found in patients. Conversely, in the airways TRAIL positively regulates inflammation and immune response. In COPD patients and asthmatic patients challenged with antigen, TRAIL and its death receptors are upregulated in serum and airways. Furthermore, TRAIL-deleted mouse models have reduced airway inflammation and remodelling. In the context of respiratory infections, TRAIL assists in immune response, e.g., via T-cell toxicity in influenza infection, and neutrophil killing in S. pneumoniae infection. In this mini-review, we examine the functions of TRAIL and highlight the diverse roles TRAIL has in diseases affecting the lung. Disentangling the facets of TRAIL signalling in lung diseases could help in understanding their pathogenic processes and targeting novel treatments.
肿瘤坏死因子相关凋亡诱导配体（TRAIL）是一种广泛表达的细胞因子，可与五种不同的受体结合。TRAIL因其被认为具有选择性诱导肿瘤细胞凋亡的能力而备受关注。然而，人们还发现它可通过激酶信号通路调节多种非典型细胞效应，包括细胞存活、迁移和增殖。肺部疾病涵盖了影响多个组织的多种病症。TRAIL参与了肺部疾病的多个生物学过程，包括血管生成、炎症和免疫调节。例如，TRAIL在肺动脉高压中具有有害作用——它在患者血清和肺组织中上调，并在啮齿动物模型中驱动潜在的增殖性肺血管重塑。然而，在小鼠模型中TRAIL可预防肺纤维化——通过诱导中性粒细胞凋亡——并且在患者中发现血清TRAIL水平降低。相反，在气道中TRAIL可正向调节炎症和免疫反应。在慢性阻塞性肺疾病（COPD）患者和受到抗原刺激的哮喘患者中，TRAIL及其死亡受体在血清和气道中上调。此外，缺失TRAIL的小鼠模型气道炎症和重塑减轻。在呼吸道感染的情况下，TRAIL有助于免疫反应，例如在流感感染中通过T细胞毒性作用，以及在肺炎链球菌感染中杀伤中性粒细胞。在本综述中，我们研究了TRAIL的功能，并强调了TRAIL在影响肺部的疾病中的多种作用。理清TRAIL信号在肺部疾病中的各个方面可能有助于理解其致病过程并靶向新的治疗方法。
