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The following is a summary of “Increased Muc5AC and Decreased Ciliated Cells in Severe Asthma Partially Restored by Inhibition of IL-4Rα Receptor,” published in the December 2024 issue of Pulmonology by Boomer et al. 

The role of IL-13 on the airway epithelium in severe asthma and its contribution to airway remodeling had remained poorly understood. 

Researchers conducted a retrospective study to investigate the impact of IL-13 on goblet cell hyperplasia and ciliary dysfunction in the airway epithelium of patients with severe asthma and to assess the in vitro effects of dupilumab, an anti-IL4Rα antibody. 

They obtained quantitative computed tomography of the lungs, endobronchial biopsies, and brushings from 51 participants (22 with severe asthma, 11 with nonsevere asthma, and 18 healthy participants) in Severe Asthma Research Program III (SARPIII). These samples were analyzed for mucin and cilia-related proteins. Epithelial cells were differentiated at the air-liquid interface (ALI) with IL-13, with or without dupilumab, and assessed for mucin, cilia, cilia beat frequency (CBF), and epithelial integrity (transepithelial electrical resistance [TEER]). 

The results showed the biopsies from patients with severe asthma exhibited increased Muc5AC (Δ + 263.2 ± 92.7 luminosity/epithelial area) and decreased ciliated cells (Δ – 0.07 ± 0.03 Foxj1⁺ cells/epithelial area) compared to healthy controls (P < 0.01 and P = 0.047, respectively). RNA sequencing of endobronchial cell brushings confirmed an increase in Muc5AC and a decrease in a 5-gene cilia-related mean in patients with severe asthma (all P < 0.05). IL-13 (5 ng/ml)-differentiated ALI cultures from both healthy and asthmatic samples increased Muc5AC and decreased cilia (α-acetyl-tubulin) in all groups (healthy: Δ + 6.5% ± 1.5%, Δ – 14.1% ± 2.7%; asthma: Δ + 4.4% ± 2.5%, Δ – 13.1% ± 2.7%; all P < 0.001), and decreased TEER in healthy samples (-140.9 ± 21.3 [ohms], P < 0.001), while CBF decreased in asthma samples (Δ – 4.4 ± 1.7 [Hz], P < 0.01). Dupilumab addition to IL-13-treated ALI cultures did not significantly reduce Muc5AC, but restored cilia in both healthy participants (67.5% increase) and those with asthma (32.5% increase) (all P < 0.05), while CBF increased (Δ + 3.6 ± 1.1 [Hz], P < 0.001) and TEER decreased only in asthma samples (Δ – 37.8 ± 16.2 [ohms], P < 0.05). 

Investigators concluded that IL-13 played a significant role in driving airway remodeling features, such as goblet cell hyperplasia and ciliary dysfunction, in severe asthma, and the effects were partially reversed by inhibiting the IL-4Rα receptor in vitro. 

Source: pubmed.ncbi.nlm.nih.gov/38935626/