In severe eosinophilic asthma (SEA) the airway epithelium exhibits fragility, reduced integrity, and increased permeability. The combined effect of blocking the IL-5R? on eosinophils and epithelium, on lung repair and regeneration in SEA, is unexplored. Aims Determine: 1) effect of eosinophils on nasal epithelial cell (NEC) barrier function and shedding, 2) role of anti-IL5R therapy Benralizumab to restore barrier function. NEC were obtained from SEA at pre-, 1-and 6-months of Benralizumab treatment (n=6). Basal epithelial cell cultures were used to determined shedding phenotypes of NECs and presence of nasal immune cells. Basal and air-liquid interface (ALI) cultured NECs were co-cultured with blood eosinophils from SEAs or treated with IL-5 or Benralizumab; TEER and FITC-dextran assays determined epithelial cell permeability and integrity. RNAseq, qRT-PCR and western blots compared levels of junctional, goblet cell genes and IL-5R? (n=5). NEC from SEA show reduced basal shedding, increased barrier integrity (1.5-fold, p=0.04) and a reduction in nasal eosinophils (p=0.01). Basal and ALI NECs, co-cultured with eosinophils activated with IL-5 or IL-5 conditioned medium show decreased integrity (-71.9?cm2, p=0.05) and increased barrier permeability (12.6%, p=0.046), MUC5AC gene expression (1.45-fold, p=0.01) and cleaved E-cadherin protein levels (0.8-fold). ALI NECs treated with IL-5 exhibited increased barrier permeability and reduced integrity compared to vehicle and untreated cells; addition of Benralizumab after IL-5 pre-treatment dampened the effect with less leakage and increased integrity measured. Benralizumab treatment in SEA remodels nasal epithelium restoring barrier function.