1.2 Chronic rhinosinusitis (CRS)
CRS is a chronic inflammatory disease that manifests with symptoms such
as nasal congestion, hyposmia, and facial pain occurring in the mucosa
of the sinuses. CRS has a complex pathogenesis, and some patients do not
respond well to systemic medications and surgery. According to
epidemiological data, approximately 8% of all people have CRS, among
which chronic rhinosinusitis with nasal polyps (CRSwNP) accounts for
25% to 30% [10].
Due to the rapid development of updated single-cell sequencing
technology, our understanding of CRS has progessed to studying various
pathways involved in its pathogenesis. ScDNA-seq revealed that B cells
differentiate into IgE-producing B cells via IgG/IgA1-IgE class
switching, which induces an allergic reaction involving nasal bacterial
protective mucosa in CRSwNP patients [11]. In addition, epithelial
cell dysfunction, abnormal stem cell differentiation, and epithelial
cell remodeling are also important reasons for the occurrence of type 2
CRSwNP. A Pistochini et al. [12] used scRNA-seq technology to
validate genes that may be involved in the inflammatory mechanism of
CRS, and unexpectedly found that AQP5 , CAV1 , LTF ,
and MGB1 gene expression, which is potentially associated with
epithelial dysfunction, was significantly reduced in nasal polyp
patients. In 2018, researchers used the Seq Well platform to analyze the
ethmoid sinus of patients across the CRS spectrum, and described the
types of human respiratory epithelial cells, immune cells, stromal
cells, as well as the transcriptome of subtype 2 inflammatory diseases.
That was the first time that researchers found that the abnormal
differentiation tracks of stromal cells in nasal polyps led to changes
in epithelial cell diversity [13]. A recent study of RNA sequencing
cell type transcriptional characteristics data obtained from patients by
nasal sinus epithelial scrubbing found that airway epithelial remodeling
in nasal polyps was caused by cell type changes and proglandin E2 (PGE2)
[14]. The above research on epithelial cells in CRS has paved the
way for revealng the profile of the CRS endogenous transcriptome.
Finally, a single cell level analysis of immune cells and non-immune
cells in healthy individuals and heterogeneous CRS patients revealed
that of the many specific cell subsets and molecules, ALOX15+
macrophages recruit eosinophils, monocytes and Th 2 cells to participate
in the pathogenesis of eosinophilic CRS with nasal polyps (eCRSwNP) type
2 immunity by secreting chemokines [15]. Mast cells (MCs), as
sentinels of the immune system, infiltrate different MC subsets in type
2 airway allergic inflammatory diseases. These infiltrated MCs include
subepithelial MCs expressing the proteases tryptase and chymase (MCTC)
and epithelial MCs expressing tryptase without chymase (MCT). Daniel F.
Dwyer [16] used scRNA seq to perform a MC analsyis of CRWwNP, and
identified a CD38high CD17high intermediate state cell. Furthermore, the
numbers of those intermediate state cells were significantly increased
in CRSwNP patients with aspirin exacerbating respiratory disease (AERD).
Those investigators first proposed that the expanded mucosal
T2-inflammation-associated MC subsets be reclassified as airway
inflammatory MCT and MCTC (iMCT and iMCTC). The proposed existence of an
intermediate MC subtype is now crucial for the treatment of T2 type
CRSwNP with different severity levels. Thus, for therapeutic
interventions in polyposis, it may be possible to ameliorate the
development of CRS by blocking or inhibiting key MC genes with
monoclonal antibodies, and thereby altering MC proliferation and
transcriptional activity.
It goes without saying that SCS analysis of CRS provides strong
theoretical support for a further in-depth exploration CRS pathogenesis
and cell specific mechanisms.