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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. [ABSTRACT FROM AUTHOR]

A comprehensive understanding of the dynamic regulatory networks that govern postnatal alveolar lung development is still lacking. To construct such a model, we profiled mRNA, microRNA, DNA methylation, and proteomics of developing murine alveoli isolated by laser capture microdissection at 14 predetermined time points. We developed a detailed comprehensive and interactive model that provides information about the major expression trajectories, the regulators of specific key events, and the impact of epigenetic changes. Intersecting the model with single-cell RNASeq data led to the identification of active pathways in multiple or individual cell types. We then constructed a similar model for human lung development by profiling time-series human omics data sets. Several key pathways and regulators are shared between the reconstructed models. We experimentally validated the activity of a number of predicted regulators, leading to new insights about the regulation of innate immunity during lung development. [ABSTRACT FROM AUTHOR]