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The IL-4/IL-13 axis is involved in the pathogenesis of allergic rhinitis (AR). In this study, we investigated the serum cytokines levels of IL-4, IL-5, IL-6, and IL-13 in AR patients, and the transcript expression levels of their receptors ( i.e. IL4R ,  IL5RA ,  IL6R,  and  IL13RA1 ) in nasal epithelial cells of AR patients  versus  non-allergic controls. Nasal epithelial cells and blood samples of non-allergic controls ( n  = 30) and AR patients ( n  = 30) were collected to examine mRNA expression and serum cytokines levels, respectively. Bioinformatics analyses of IL-4/IL-13 receptor heterodimer association with tight junction (TJ) and JAK/STAT signaling genes were conducted in a gene expression profiling (GEP) dataset (GSE44037) of AR patients ( n  = 12) and healthy controls ( n  = 6). Serum IL-4, IL-5, IL-6 or IL-13 levels, and  IL13RA1  transcript expression were significantly higher in AR patients compared with non-allergic controls. IL-4 and IL-13 serum levels were positively correlated with  IL13RA1  expression in AR patients but not in non-allergic controls. In the GEP dataset (GSE44037), six TJ ( CLDN4 ,  CLDN7 ,  CLDN12 ,  CLDN15 ,  TJP1 , and  TJP2 ) genes’ expressions were negatively correlated, respectively, with IL-4Rα/IL-13Rα1 heterodimeric receptor expression in AR patients and not in control samples. These six TJ genes contributed to the significant enrichment of tight junction Gene Ontology (GO ID: 0070160). Lastly, STATs DNA binding motif analysis showed that each of these TJ genes contains STATs binding consensus sequence within intronic and intergenic regions. Our results suggest that increased IL-4/IL-13 serum cytokines levels may contribute to decreased TJs expression via IL-4Rα/IL-13Rα1 heterodimeric receptor in nasal epithelium of AR patients.

IL-4/IL-13 Axis in Allergic Rhinitis: Elevated Serum Cytokines Levels and Inverse Association With Tight Junction Molecules Expression