Section of Pulmonary, Critical Care, and Sleep Medicine, Yale School of Medicine, Yale University, New Haven, Connecticut.
Am J Physiol Lung Cell Mol Physiol. 2022 Apr 1;322(4):L518-L525. doi: 10.1152/ajplung.00266.2021. Epub 2022 Feb 23.
Sarcoidosis is a chronic granulomatous disease of unknown etiology that primarily affects the lungs. The development of stage IV or fibrotic lung disease accounts for a significant proportion of the morbidity and mortality attributable to sarcoidosis. Further investigation into the active mechanisms of disease pathogenesis and fibrogenesis might illuminate fundamental mediators of injury and repair while providing new opportunities for clinical intervention. However, progress in sarcoidosis research has been hampered by the heterogeneity of clinical phenotypes and the lack of a consensus modeling system. Recently, reverse translational research, wherein observations made at the patient level catalyze hypothesis-driven research at the laboratory bench, has generated new discoveries regarding the immunopathogenic mechanisms of pulmonary granuloma formation, fibrogenesis, and disease model development. The purpose of this review is to highlight the promise and possibility of these novel investigative efforts.
结节病是一种病因不明的慢性肉芽肿性疾病,主要影响肺部。第四阶段或纤维化肺病的发展是结节病发病率和死亡率的重要原因。进一步研究疾病发病机制和纤维化形成的活跃机制可以阐明损伤和修复的基本介质,同时为临床干预提供新的机会。然而,结节病研究的进展受到临床表型的异质性和缺乏共识建模系统的阻碍。最近,反向转化研究,即患者层面的观察结果促进实验室研究的假设驱动研究,已经发现了关于肺肉芽肿形成、纤维化和疾病模型发展的免疫发病机制的新发现。本文的目的是强调这些新的研究努力的潜力和可能性。