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This study investigates the function of cathepsin C in the nasal epithelium and its role in type 2 inflammation.

March 13, 2026Journal of Inflammation Research0 citationsOpen Access

Inhibition of Airway Epithelial CTSC Attenuates Type 2 Inflammation: Implications for Eosinophilic Chronic Rhinosinusitis with Nasal Polyps

Key Points

This study investigates the function of cathepsin C in the nasal epithelium and its role in type 2 inflammation.
Enrolled patients with eosinophilic and non-eosinophilic chronic rhinosinusitis and controls.
Examined airway epithelial morphology using scanning electron microscopy.
Analyzed CTSC expression through scRNA-seq, immunohistochemistry, and quantitative PCR.
Conducted in vitro studies using an IL-4/IL-13-stimulated 16HBE cell line model.
CTSC is primarily localized in goblet and basal cells of the nasal epithelium.
CTSC expression is significantly elevated in eosinophilic chronic rhinosinusitis patients.
CTSC expression correlates positively with T-helper 2 cytokines (IL-4, IL-13).
Knockdown of CTSC reduces inflammatory cytokine release (CCL26, IL-25, TNF-α).

Abstract

Purpose: Cathepsin C (CTSC) has been identified as a key pathogenic gene in chronic rhinosinusitis. This study aimed to investigate the specific function and subcellular localization of CTSC within the nasal mucosal epithelium. Patients and Methods: A total of 34 patients with eosinophilic chronic rhinosinusitis with nasal polyps (eNP), 32 with non-eosinophilic chronic rhinosinusitis with nasal polyps (neNP), and 16 control subjects were enrolled. Airway epithelial morphology was examined by scanning electron microscopy. The expression, localization, and function of CTSC in epithelial cells were assessed using single-cell RNA sequencing (scRNA-seq), immunohistochemistry, quantitative real-time PCR, Western blot, and an siRNA-mediated knockdown approach in an IL-4/IL-13-stimulated 16HBE cell line model. Results: scRNA-seq revealed that CTSC was primarily localized to goblet cells and basal cells within the nasal epithelium, with its expression significantly upregulated in eNP patients compared with those in control subjects and neNP. These findings were confirmed at both the RNA and protein levels in clinical tissue samples. CTSC mRNA expression showed a significant positive correlation with the expression of T-helper 2 cytokines, including IL-4 and IL-13. In vitro experiments demonstrated that CTSC expression was induced in 16HBE cells upon IL-4/IL-13 stimulation. siRNA-mediated knockdown of CTSC led to pronounced suppression of IL-4/IL-13-induced release of CCL26, IL-25 , and TNF-α , underscoring its functional involvement in inflammatory responses. Conclusion: This study identifies CTSC as a novel regulator of type 2 inflammation like eNP. It is specifically upregulated in nasal epithelial goblet and basal cells, highlighting its potential as a therapeutic target for airway diseases. Keywords: Cathepsin C, eosinophilic chronic rhinosinusitis with nasal polyps, type 2 inflammation, epithelial cells

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