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Single-cell RNA sequencing of immune cells involved in asthma attacks
A study provides insight into the immune response involved in asthma exacerbation. Asthma exacerbations, or asthma attacks, are the major cause of asthma-related hospitalizations and the primary source of asthma-related healthcare costs. Asthma exacerbations resist standard glucocorticoid-based therapy and are triggered by a variety of factors. Ming Yang, Fuguang Li, and colleagues used single-cell RNA deep sequencing to undertake a large-scale, high-dimensional analysis of the lung immune response in a mouse model of asthma exacerbation. The authors identified 20 major clusters of immune cells in the lungs of these mice based on gene expression profiles at the single-cell level. Interleukin-13 (IL-13), a key mediator of allergic inflammation, was highly expressed by CD8+ memory T cells, basophils, and type 2 innate lymphoid cells during asthma exacerbation relative to non-asthmatic controls, and was insensitive to glucocorticoid treatment. Neutralizing IL-13 using antibodies abolished lipopolysaccharide-induced airway hyperresponsiveness and inflammation and reduced mucus hypersecretion in asthmatic mice, suggesting that IL-13 is essential for steroid-resistant asthma exacerbation. The authors identified multiple steroid-resistant signaling pathways regulating the activation of IL-13-producing cells. The results provide insight into the immune landscape of the lungs during asthma exacerbation and could guide the development of cell-targeted therapies, according to the authors.