This study evaluated the IL-9/Arginase-1 (Arg1)/polyamine pathway in human airway macrophages using humanized NSG-Quad mice treated with intranasal IL-9 and bronchoalveolar lavage (BAL) samples from asthmatic and healthy control patients, assessed via flow cytometry, bulk RNA sequencing, and metabolic assays.
IL-9 drove expansion of IL-9R+/Arg1+ CD43− macrophages in humanized mice and in asthmatic patient BAL compared to healthy controls; polyamine concentrations in BAL were elevated in asthma and positively correlated with BAL IL-9 levels and IL-9R+/Arg1+ CD43− macrophage proportions.
- Humanized mouse models may not fully replicate human airway macrophage biology. - Causal direction between IL-9, macrophage phenotype, and polyamine levels cannot be established from correlational BAL data. - Sample sizes for patient BAL cohorts are not reported in the abstract.
The IL-9R/Arg1/polyamine axis in CD43− airway macrophages appears active in asthma, identifying this pathway as a potential therapeutic target. Clinicians should watch for emerging treatments aimed at IL-9 or downstream polyamine metabolism in asthma management.
