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IL‐13 signaling through IL‐13 receptor α2 mediates airway epithelial wound repair
Author(s) -
Yang S. Jasemine,
Allahverdian Sima,
Saunders Angela D. R.,
Liu Emily,
Dorscheid Delbert R.
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201801285r
Subject(s) - airway , epidermal growth factor , cytokine , signal transduction , wound healing , interleukin 13 , epidermal growth factor receptor , receptor , microbiology and biotechnology , epithelium , respiratory epithelium , immunology , interleukin , biology , medicine , cancer research , pathology , surgery
Asthma is an airway inflammatory disease characterized by epithelial barrier dysfunction and airway remodeling. Interleukin‐13 (IL‐13) is a pleiotropic cytokine shown to contribute to features of airway remodeling. We have previously demonstrated that IL‐13 is an important mediator of normal airway epithelial repair and health. The role of IL‐13 signaling via its receptor subunits (IL‐13Rα1/IL‐4Rα and IL‐13Rα2) in airway epithelial repair and restoration of intact barrier function is not well understood and was investigated in this study using in vitro models. The blocking of IL‐13 signaling via IL‐13Rα2 significantly reduced airway epithelial repair by 24 h post‐mechanical wounding in 1HAEo − cells. Expression and release of repair‐mediating growth factor, heparin‐binding epidermal growth factor (EGF)‐like growth factor (HB‐EGF), and subsequent activation of EGF receptor (EGFR) were also significantly reduced in response to wounding when IL‐13Rα2 was blocked. Our data support that IL‐13 signals via IL‐13Rα2 to mediate normal airway epithelial repair via HB‐EGF‐dependent activation of EGFR. In human donor lung tissues, we observed that airway epithelium of asthmatics expressed significantly decreased levels of IL‐13Rα2 and increased levels of IL‐13Rα1 compared with nonasthmatics. Dysregulated expression of IL‐13 receptor subunits in the airways of asthmatics may thus contribute to the epithelial barrier dysfunction observed in asthma.—Yang, S. J., Allahverdian, S., Saunders, A. D. R., Liu, E., Dorscheid, D. R. IL‐13 signaling through IL‐13 receptor α2 mediates airway epithelial wound repair. FASEB J. 33, 3746–3757 (2019). www.fasebj.org