A single-cell atlas of the human airways from patients with allergic rhinitis comorbid with asthma.

BACKGROUNDSingle-cell RNA profiling has already been applied to normal airway samples, but no data set includes brushings collected from patients with allergic rhinitis combined with asthma (ARcoAS) at distinct and well-identified microanatomical regions in the airways.

OBJECTIVETo investigate cell population distributions and transcriptional changes along the upper and lower airways of patients with ARcoAS by using single-cell RNA profiling.

METHODSNasal and bronchial brush cells from patients with ARcoAS and healthy volunteers were collected for single-cell RNA sequencing analysis. The cellular clusters, differential gene analysis, cellular pathway enrichment, mimetic temporal analysis, and cellular communication were analyzed between the nasal and bronchial airways.

RESULTSA similar alteration in the cell profiles of the upper and lower airways was observed under chronic inflammatory conditions. A total of 3613 (57%) shared up-regulated genes, and 5410 (66%) shared down-regulated genes were identified between the upper and lower airways of ARcoAS. Impaired structure of ciliated cells and epithelial barrier was observed in diseased nasal and bronchial airways. The intercellular communication analysis revealed a decreased number and strength of intercellular interactions between epithelial cells and immune cells in the ARcoAS group. We found that the GZMA-PARD3 pathway disrupts the airway epithelial barrier in vitro.

CONCLUSIONOur findings suggest that compromised ciliated cells and aberrant proliferation of basal cells may drive eosinophilic inflammation in response to type 2 inflammation in patients with ARcoAS. Robust characterization of a single-cell cohort in allergic airways establishes a valuable resource for future investigations and provides potential targets for tailored treatment.