Impact of the cytokine milieu on fibroblasts and their characterization in chronic rhinosinusitis with nasal polyps

Nasal polyps (NP) contribute to treatment resistance in chronic rhinosinusitis with nasal polyps (CRSwNP); however, the cellular and molecular mechanisms underlying nasal polypogenesis are not completely understood. To investigate whether the characteristics of fibroblasts differ under the surrounding tissue environment. Patients with CRSwNP were divided into two groups based on the eosinophil infiltration in the NP; the gene expression levels were evaluated. Fibroblasts established from NP were assessed for functional changes following cytokine stimulation, and RNA sequencing (RNA-seq) was performed. IL5 and IL13 expression was higher, and IFNG and TNF lower, in NP from eosinophilic CRS (ECRS) patients compared to non-ECRS. FOXP3 expression was significantly upregulated in ECRS patients. Cytokine-stimulated fibroblasts from both ECRS and non-ECRS showed similar expression of fibroblast-to-myofibroblast transition-related genes and significantly reduced migratory capacity following IL-13 and TNF-α treatment. RNA sequencing revealed six and thirty-five significant activated and inactivated signaling pathways, respectively, in the Diseases Bio Functions analysis. Fibroblasts contribute to nasal polypogenesis irrespective of inflammation type in CRSwNP. Although their behavior is regulated by the immune microenvironment, our findings also highlight fibroblasts as potential therapeutic targets, supporting both endotypic classification and novel treatment strategies.