biostudies-literatureLiegeois MANational Science Foundation Graduate Research Fellowship ProgramNIAID NIH HHSNHLBI NIH HHSNIAIDNIH HHSCystic Fibrosis TrustNIH National Heart Lung and Blood Institutee181024https://www.ebi.ac.uk/biostudies/studies/S-EPMC11383604biostudies-literatureUnknown9(15)Mucus plugs occlude airways to obstruct airflow in asthma. Studies in patients and in mouse models show that mucus plugs occur in the context of type 2 inflammation, and studies in human airway epithelial cells (HAECs) show that IL-13-activated cells generate pathologic mucus independently of immune cells. To determine how HAECs autonomously generate pathologic mucus, we used a magnetic microwire rheometer to characterize the viscoelastic properties of mucus secreted under varying conditions. We found that normal HAEC mucus exhibited viscoelastic liquid behavior and that mucus secreted by IL-13-activated HAECs exhibited solid-like behavior caused by mucin cross-linking. In addition, IL-13-activated HAECs shows increased peroxidase activity in apical secretions, and an overlaid thiolated poJCI insightPeroxidase-mediated mucin cross-linking drives pathologic mucus gel formation in IL-13-stimulated airway epithelial cells.PMC11383604NAU19 AI077439P01 HL107202R01 HL080414HL080414,HL107202S10 OD028611R01 HL164787AI077439Moore WCWenzel SEBraunreuther MCastro MWoodruff PGFuller GGFahy JVCharbit ARLevy BDRaymond WWJarjour NNTang MIsrael EErzurum SCLiegeois MAChristenson SAfalsePeroxidase-mediated mucin cross-linking drives pathologic mucus gel formation in IL-13-stimulated airway epithelial cells.Mucus plugs occlude airways to obstruct airflow in asthma. Studies in patients and in mouse models show that mucus plugs occur in the context of type 2 inflammation, and studies in human airway epithelial cells (HAECs) show that IL-13-activated cells generate pathologic mucus independently of immune cells. To determine how HAECs autonomously generate pathologic mucus, we used a magnetic microwire rheometer to characterize the viscoelastic properties of mucus secreted under varying conditions. We found that normal HAEC mucus exhibited viscoelastic liquid behavior and that mucus secreted by IL-13-activated HAECs exhibited solid-like behavior caused by mucin cross-linking. In addition, IL-13-activated HAECs shows increased peroxidase activity in apical secretions, and an overlaid thiolated po2024-01-01T00:00:00Z2024 Jun2026-05-02T12:45:08.133Z2025-04-04T00:29:54.178ZS-EPMC113836043888904610.1172/jci.insight.181024