1.3 Asthma
Asthma is considered as a respiratory disease characterized by chronic airway inflammation that involves a variety of cells (eosinophils, mast cells, T lymphocytes, neutrophils, airway epithelial cells) and cellular components. It is associated with airway hyper-reactivity, and usually with widespread and variable reversible expiratory airflow restriction which can lead to recurrent symptoms such as wheezing, shortness of breath, chest tightness and cough, with the intensity varying over time [17]. The phenotype of asthma can be divided into exogenous, endogenous and mixed asthma based on different clinical manifestations, pathophysiological characteristics, and prognostic differences [18]. The interaction of inflammatory cells with the external environment results in airway inflammation, airflow restriction, hyperreactivity, and airway remodeling during the pathologic progression of asthma. At present, the pathogenesis of asthma is not clearly defined.
The current applications of SCS in asthma have mainly focused on immune cells and lung epithelial cells involved in its pathogenesis. Researchers have used scRNAseq to analyze subsets of lung immune cells in an asthma mouse model induced by the house dust mite (HDM). The results identified 20 immune subsets and revealed that basophils, type 2 congenital lymphocytes (ILC2), and CD8+specific cell clusters Memory T cells were the main sources of IL-4 and IL-13 [19, 20]. Subsequent studies used scRNA-seq and scATAC-seq to sequence alveolar lavage fluid from asthma patients and found that the Foxp3+Treg, Th1, Th2, and Th17 cell subpopulations were significantly increased, and the characteristic genes of Th2 cells were mainly Cd200r1 , Il6 , Plac8 , and Igfbp7 . Moreover, a differentiation disorder of T cells was found to lead to a Th1/Th2 imbalance, and the development and occurrence of asthma [21]. As antigen-presenting cells, DCs play an important role in the allergen-driven Th2 immune response in asthmatic airways. Gentaro Izumi et al. [22] identified 5 distinct lung conventional CD11b+ DCs (cDC2) clusters by use of scRNA-Seq technology, and found that lung cDC2 promoted Th17 and Th2 differentiation at different maturation stages. Li et al. [23] used scRNA-seq to show that neutrophils promoted the uptake of allergens by lung CD11b+Ly-6C+DC and increased susceptibility to exacerbated asthma in the lung tissues of asthmatic mice. The key immune cell phenotypes of patients with asthma exacerbation mainly include monocytes, CD8+T cells and macrophages, and investigators have clearly proposed candidate genes that are closely related to asthma exacerbation [24]. Lung epithelial cells are important for maintaining stable lung structure. ScRNA-seq revealed that IL-1β produced by human airway epithelial cells increases airway mucus concentrations by inducing HAEC to release MUC5B, leading to airway remodeling and pathogenic mucus hypersecretion in asthma [25]. Subsequent studies discovered a new type of ciliated epithelial cell related to asthma, and proved that epithelial cell dysfunction with increased goblet cell and mucus production was the initial pathologic factor in asthma [26]. SCS studies of asthma have provided new insights into the role of epithelial and immune cell function in epithelial cell remodeling in asthma.