For a study, it was determined that Cystic fibrosis (CF) was a multisystem genetic disease with a life-shortening effect caused by faulty chloride transport. Innate immune dysfunction and increased inflammatory responses led to tissue harm in CF lung disease. Researchers completed the first single-cell transcriptome characterization of CF sputum to establish the transcriptional signature of this airway immune dysfunction. To determine the transcriptional profile of sputum cells and its relevance to immune function pathogenesis and the progression of CF lung disease. They did Single-cell RNA sequencing on sputum cells from nine CF patients and five healthy controls. They used unique computational methodologies to establish expression-based cell function and maturity profiles to establish transcriptional archetypes.
In CF, the airway immune cell repertoire moved from alveolar macrophages to recruited monocytes and neutrophils, whereas in healthy control participants, it was alveolar macrophages. CF patients had an abundance of recruited lung mononuclear phagocytes, which have three archetypes: activated monocytes, monocyte-derived macrophages, and heat shock–activated monocytes. Neutrophils were the most common kind of cell in CF, with an immature proinflammatory phenotype dominating. Although CF monocytes were proinflammatory, transcriptional evidence of aberrant phagocytic and cell-survival pathways in both monocytes and neutrophils. The findings provide a window into subject-specific immune dysfunction and how it contributes to CF patients’ differing clinical outcomes. They expect that the inflammation-profiling technique will enable subsequent discoveries that affect the natural history of CF lung disease as they proceed toward tailored applications of pharmacological and genetic developments.