Birmingham Acute Care Research Group, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, United Kingdom.
NIHR Clinical Research Facility Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom.
Front Immunol. 2021 Jul 21;12:704173. doi: 10.3389/fimmu.2021.704173. eCollection 2021.
Infection and inflammation of the lung results in the recruitment of non-resident immune cells, including neutrophils, eosinophils and monocytes. This swift response should ensure clearance of the threat and resolution of stimuli which drive inflammation. However, once the threat is subdued this influx of immune cells should be followed by clearance of recruited cells through apoptosis and subsequent efferocytosis, expectoration or retrograde migration back into the circulation. This cycle of cell recruitment, containment of threat and then clearance of immune cells and repair is held in exquisite balance to limit host damage. Advanced age is often associated with detrimental changes to the balance described above. Cellular functions are altered including a reduced ability to traffic accurately towards inflammation, a reduced ability to clear pathogens and sustained inflammation. These changes, seen with age, are heightened in lung disease, and most chronic and acute lung diseases are associated with an exaggerated influx of immune cells, such as neutrophils, to the airways as well as considerable inflammation. Indeed, across many lung diseases, pathogenesis and progression has been associated with the sustained presence of trafficking cells, with examples including chronic diseases such as Chronic Obstructive Pulmonary Disease and Idiopathic Pulmonary Fibrosis and acute infections such as Pneumonia and Pneumonitis. In these instances, there is evidence that dysfunctional and sustained recruitment of cells to the airways not only increases host damage but impairs the hosts ability to effectively respond to microbial invasion. Targeting leukocyte migration in these instances, to normalise cellular responses, has therapeutic promise. In this review we discuss the current evidence to support the trafficking cell as an immunotherapeutic target in lung disease, and which potential mechanisms or pathways have shown promise in early drug trials, with a focus on the neutrophil, as the quintessential trafficking immune cell.
肺部的感染和炎症会导致非驻留免疫细胞的募集，包括中性粒细胞、嗜酸性粒细胞和单核细胞。这种快速反应应该确保清除威胁，并解决驱动炎症的刺激因素。然而，一旦威胁得到控制，这些免疫细胞的涌入应该通过细胞凋亡和随后的吞噬作用、咳出或逆行迁移回循环来清除募集的细胞。这种细胞募集、威胁控制以及免疫细胞和修复的清除的循环被精确地平衡，以限制宿主损伤。高龄通常与上述平衡的不利变化有关。细胞功能发生改变，包括向炎症准确迁移的能力降低、清除病原体的能力降低和持续的炎症。这些随着年龄增长而出现的变化在肺部疾病中更为明显，大多数慢性和急性肺部疾病都与免疫细胞（如中性粒细胞）向气道的过度涌入以及相当大的炎症有关。事实上，在许多肺部疾病中，发病机制和进展都与趋化细胞的持续存在有关，例如慢性阻塞性肺疾病和特发性肺纤维化等慢性疾病以及肺炎和肺炎等急性感染。在这些情况下，有证据表明，细胞向气道的功能失调和持续募集不仅增加了宿主损伤，还损害了宿主有效应对微生物入侵的能力。在这些情况下，靶向白细胞迁移以使其细胞反应正常化具有治疗前景。在这篇综述中，我们讨论了支持将趋化细胞作为肺部疾病免疫治疗靶点的现有证据，以及哪些潜在的机制或途径在早期药物试验中显示出了希望，重点是中性粒细胞，作为典型的趋化免疫细胞。
