Inflammatory and homeostatic roles of eosinophil subpopulations in chronic rhinosinusitis with nasal polyp pathogenesis

Abstract

Chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) mainly expresses type-2 endotype, featuring eosinophils as a main player in the inflammatory process. Prolonged eosinophilia in the tissues of asthma and CRSwNP patients has been associated with structural changes, leading to fixed airflow obstruction in asthma and nasal polyposis in CRSwNP. This suggests that eosinophils may belong to different subgroups playing distinct roles in pathogenesis. Recent studies highlight the roles of inflammatory eosinophils (iEOS) in driving inflammation and tissue damage, whereas tissue-resident eosinophils (rEOS) maintain homeostasis and tissue repair in the airway. Therefore, understanding both roles of eosinophil subpopulations is crucial for better CRSwNP management, including enhancing the diagnosis accuracy, predicting recurrence, and optimizing treatment strategies.

Keywords: chronic rhinosinusitis with nasal polyps; eosinophil; eosinophil subpopulations; inflammatory eosinophils; resident eosinophils.

Figure 1

The different role of eosinophil subgroups in chronic inflammatory diseases The increase of pro-inflammatory cytokines from the inflamed areas induces the eosinophil progenitors to proliferate, mature, and differentiate into rEOS and iEOS before entering the bloodstream. Eosinophils are directed to the site of inflammation by chemokines. Their movement becomes slower and trapped by the elevated expression of adhesion molecules on epithelial cells before penetrating into the inflamed site. Within this microenvironment, eosinophils become activated and release cytokines and granules, contributing to pathogenesis and adverse outcomes in diseases such as CRSwNP, asthma, EoE, and EGPA. To create a strategy for managing these diseases, several technology facilitates the investigation of the differences in eosinophil function in individuals. Figure created with www.BioRender.com ACQ, Asthma Control Questionnaire; ACT, Asthma Control Test; EGPA, Eosinophilic granulomatosis with polyangiitis; EoE, Eosinophilic Esophagitis; EoEHSS, Eosinophilic Esophagitis Histologic Scoring System EoP, Eosinophil progenitors; FFS, Five-factor score; I-SEE, Index of Severity for Eosinophilic Esophagitis; iEOS, inflammatory eosinophil; MLK, Modified Lund Mackey; MLM, Modified Lund Kenedy; rEOS, resident eosinophil; SNOT-22, Sino-nasal Outcome Test-22.

Figure 2

Novel treatment in CRSwNP specific to eosinophil function Current biological treatments approved for CRSwNP treatment. Some drugs may have a potential effect as therapeutics targeting eosinophil functions. Additionally, combining these drugs may enhance efficacy, particularly in patients who do not respond to current treatments. Figure created with www.BioRender.com .