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.