Progress in cellular mechanisms of chronic rhinosinusitis

Chronic rhinosinusitis (CRS) represents one of the most common chronic conditions occurring in the nasal cavity and sinuses, affecting approximately 10% of the global population and imposing a significant socioeconomic burden. The introduction of novel methodologies, notably single-cell sequencing, has unveiled the extensive heterogeneity of structural cells and immune cells, significantly enhanced our understanding of CRS pathogenesis and facilitated the development of more precise diagnostic and therapeutic approaches. Dysfunction of the epithelial barrier, inflammatory memory stored within the epithelium, and the heightened interactions between epithelial cells and immune cells have been implicated in playing pivotal roles in CRS pathogenesis. Emerging evidence highlights the critical role of local immunoglobulin overproduction in CRS. Within ectopic lymphoid tissues (eLTs), a dynamic interplay exists where follicular helper T (Tfh) cells facilitate, while follicular regulatory T (Tfr) cells inhibit, the production of immunoglobulins. Conversely, PD-1^highCXCR5^- T cells are capable of promoting immunoglobulin production independent of eLTs. Importantly, the ongoing immunoglobulin class-switch recombination to IgE has been observed in polyp tissues. Additionally, accumulating evidence has highlighted the significant contributions of macrophages and mast cells in driving type 2 immunity in eosinophilic CRS, positioning these cells as potential therapeutic targets. The enhanced understanding of structural and immune cell dynamics in CRS not only sheds light on the intricate pathophysiological mechanisms underlying the condition but also inspires the pursuit of innovative treatments aimed at recalibrating the complex interactions within the immune landscape of CRS patients.