Identification of Type 2-pediatric Asthma Based on Single-cell Transcriptomic Analysis

Abstract Type 2-pediatric asthma characterized by T2 cytokine-driven airway inflammation is the most common type of asthma. Recently, T2 cytokine inhibitors have reduced the exacerbation rates of asthma, but their ability to improve lung function is limited. Screening novel therapeutic strategies for Type 2-pediatric asthma patients is imperative. We obtained single-cell RNA sequencing (scRNA-seq) describing the chronic stimulation GSE145013 dataset with IL-13. Consensus clustering was performed to classify pediatric asthmatic patients from validation datasets GSE65204 and GSE40888, based on the cell marker genes. We found three cellular subtypes including ciliated cells, secretory cell 1, and secretory cell 2. The expression of CCL26, PRB1, and SLC9B2 was higher in secretory cell 1, while SCGB3A1 and BPIFA1 were higher in secretory cell 2. Consensus clustering based on the five cell marker genes produced two patient subtypes (C1 and C2). The expression of SCGB3A1 and BPIFA1 was higher in C2 subtypes, while CCL26, PRB1, and SLC9B2 was higher in C1 subtypes. Patients in C2 subtypes may more secretory cell 2, while the patients in C1 may have higher secretory cell 1 in the infiltrate. More Type 2 T helper cells were in the infiltrate in the C2 subtype, while type 1 T helper cells were higher in the C1 subtype. T2 cytokines (IL-13, IL-33, IL-3, IL-4, and TSLP) were expressed more in the C2 subtype, corresponding to Type 2-pediatric asthma. This study identified five cell marker genes to screen Type 2-pediatric asthma that could potentially be therapeutic targets for Type 2-pediatric asthma.