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.