Unveiling CLC as a Central Regulator of Allergic Rhinitis via the CLC ‐ CCL26 / POSTN Axis: An Integrated Bioinformatics and Experimental Study

ABSTRACT Allergic rhinitis (AR) is a chronic airway inflammation driven by a type 2 immune response, yet the molecular mechanisms underlying its persistence and tissue remodelling remain incompletely understood. This study employed an integrated bioinformatics and experimental approach to systematically investigate the role of CLC (Charcot‐Leyden crystal protein/Galectin‐10) in AR pathogenesis. We identified CLC as a central hub gene through combined Weighted Gene Co‐expression Network Analysis (WGCNA) and machine learning (LASSO (Least Absolute Shrinkage and Selection Operator), SVM‐RFE (Support Vector Machine‐Recursive Feature Elimination)) of the GSE45323 dataset. Immune infiltration analysis revealed a strong positive correlation between CLC expression and M0 macrophage infiltration. Functional validation in IL‐4‐stimulated human nasal epithelial cells demonstrated that CLC knockdown significantly suppressed the expression of CCL26 (a potent eosinophil chemoattractant) and POSTN (a key mediator of tissue remodelling). This finding was corroborated in an OVA‐induced murine AR model, where CLC was markedly upregulated in nasal mucosa. Our results reveal a novel CLC‐CCL26/POSTN axis that concurrently orchestrates inflammatory cell recruitment and structural remodelling in AR, positioning CLC as a promising therapeutic target for intercepting disease progression.