Abstract / Summary
Abstract Background Interleukin-13 (IL-13) drives epithelial remodeling in allergic rhinitis (AR), but the IL-13-responsive epithelial program and its associated non-coding RNA layer in the nasal mucosa remain incompletely defined. Methods and results Two public nasal epithelial transcriptomic cohorts, GSE19187 (14 AR, 11 controls) and GSE43523 (7 seasonal AR, 5 controls), were re-analyzed, and RPMI 2650 nasal epithelial cells were stimulated with IL-13 (50 ng/mL, 24 h). Eighty-nine differentially expressed genes were identified in GSE19187. Cystatin SN (CST1) was the most strongly upregulated gene (log 2 fold change 6.00; adjusted P = 6.8 × 10 − 5 ) and distinguished AR from controls in both GSE19187 (area under the curve [AUC] 0.981) and GSE43523 (AUC 0.914). Crosslinking immunoprecipitation-supported interactions in ENCORI suggested a candidate competing endogenous RNA (ceRNA) network in which the long non-coding RNAs (lncRNAs) GAS5 and NEAT1 converged on miR-221-3p, a predicted regulator of periostin (POSTN) and SERPINB2. In RPMI 2650 cells, IL-13 increased signal transducer and activator of transcription 6 (STAT6) phosphorylation and CST1, POSTN, SERPINB2 and mucin 5AC protein levels. IL-13 also increased GAS5, MALAT1 and NEAT1 and decreased miR-221-3p, together with increased POSTN and SERPINB2 mRNA. Conclusions CST1 is a reproducible AR-associated nasal epithelial marker that is induced by IL-13 alongside STAT6 activation. IL-13 also elicits a non-coding RNA expression pattern consistent with a candidate lncRNA–miR-221-3p–POSTN/SERPINB2 axis; direct RNA–RNA binding and causal ceRNA activity remain to be established.